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Analysis of TLR4 early signaling pathways in COX inhibited macrophages. Panel A: Phospho-IκBα, total IκBα, phospho-p65, total p65 and actin protein levels from whole cell lysates were detected by Western blotting. Macrophages were differentiated for 7 days in the presence of NS-398 or indomethacin and compared with the control at the indicated time points after LPS stimulation. Each compared lanes for one protein all come from same blots. Panel B: NF-κB inhibitor (20 ng/ml) was treated to chronically NS-398 or indomethacin treated macrophages 30 min before LPS stimulation. LPS was treated at 100 ng/ml and culture medium was collected after 4 h incubation for analysis. Results represent means ± SE of three experiments. Statistical analysis was performed by one-way ANOVA. *P<0.05, **P<0.005.
Source publication
Macrophages play important roles in defense against infection, as well as in homeostasis maintenance. Thus alterations of macrophage function can have unexpected pathological results. Cyclooxygenase (COX) inhibitors are widely used to relieve pain, but the effects of long-term usage on macrophage function remain to be elucidated. Using bone marrow-...
Contexts in source publication
Context 1
... and culture medium was collected after 4 h (TNFα) and 24 h (IL-12p70 and IL-10) incubation for analysis. Results represent means ± SE of three independent experiments. Statistical analysis was performed by one-way ANOVA. *P<0.05, ***P<0.001. examined phospho-IκBα and phospho-p65 from whole cell lysates after LPS stimulation using Western blotting (Fig. 2A). Accordingly, both chronic COX-2 as well as COX-1/2 inhibited macrophages exhibited reduced total IκBα, as well as enhanced p65 phosphoylation upon LPS stimulation compared with the control. Enhanced NF-κB activity directly connected to TNFα production ability because enhanced TNFα productions were recovered when NF-kB inhibitor was ...
Context 2
... inhibited macrophages exhibited reduced total IκBα, as well as enhanced p65 phosphoylation upon LPS stimulation compared with the control. Enhanced NF-κB activity directly connected to TNFα production ability because enhanced TNFα productions were recovered when NF-kB inhibitor was treated before LPS stimulation in NS-398 and indomethacin groups (Fig. 2B). Collectively, these results indicated that macrophages lacking COXs activities during differentiation are more immune activated. ...
Similar publications
Inflammation is the first step that leads to inflammatory cell migration, cytokine release, and myofibroblast formation. Myofibroblasts can deposit excess amounts of extracellular matrix. Cyclooxygenase (COX) inhibitor exhibits strong anti-inflammatory response; however, this is usually achieved with undesirable side effects. In this study, we demo...
Citations
... This strategy will enhance M1 macrophages and therefore activate Th1 cytotoxic T cells [102]. Different polarization targets of TAMs have been studied in which the most common ones are toll-like receptor (TLR) (NF-кB/IRF3 pathway) [103,104], CSF1 (NF-кB/ERK1/2 pathway) [105], cd40 (NF-кB pathway) [ (TREM-1/DAP12/Syk pathway) [108], BTK [109] and COX2 (Blocks PI3K/AKT) [110]. TLR agonist-loaded NPs have shown promising results especially when combined with immune checkpoint inhibitors (anti-PD1) in tumor regression and improvement of the immunotherapeutic effects [110,111]. ...
... Different polarization targets of TAMs have been studied in which the most common ones are toll-like receptor (TLR) (NF-кB/IRF3 pathway) [103,104], CSF1 (NF-кB/ERK1/2 pathway) [105], cd40 (NF-кB pathway) [ (TREM-1/DAP12/Syk pathway) [108], BTK [109] and COX2 (Blocks PI3K/AKT) [110]. TLR agonist-loaded NPs have shown promising results especially when combined with immune checkpoint inhibitors (anti-PD1) in tumor regression and improvement of the immunotherapeutic effects [110,111]. Galstyan et al. [112] designed nanoscale immunoconjugate with a drug carrier called poly (β-L-malic acid), which is used to deliver covalently coupled cytotoxic T-lymphocyte-associated antigen 4 and programmed cell death-1 (PD-1) antibodies to brain tumor cells, resulting in the activation of the local immune system and extended survival of intracranial GBM GL261-bearing mice. This study [112] showed that trans-blood-brain barrier (BBB) administration of tumor-targeted checkpoint inhibitors is an effective GBM therapy by activating both local and systemic brain tumor immune responses. ...
Brain cancer is an aggressive type of cancer with poor prognosis. While the immune system protects against cancer in the early stages, the tumor exploits the healing arm of inflammatory reactions to accelerate its growth and spread. Various immune cells penetrate the developing tumor region, establishing a pro-inflammatory tumor milieu. Additionally, tumor cells may release chemokines and cytokines to attract immune cells and promote cancer growth. Inflammation and its associated mechanisms in the progression of cancer have been extensively studied in the majority of solid tumors, especially brain tumors. However, treatment of the malignant brain cancer is hindered by several obstacles, such as the blood-brain barrier, transportation inside the brain interstitium, inflammatory mediators that promote tumor growth and invasiveness, complications in administering therapies to tumor cells specifically, the highly invasive nature of gliomas, and the resistance to drugs. To resolve these obstacles, nanomedicine could be a potential strategy that has facilitated advancements in diagnosing and treating brain cancer. Due to the numerous benefits provided by their small size and other features, nanoparticles have been a prominent focus of research in the drug-delivery field. The purpose of this article is to discuss the role of inflammatory mediators and signalling pathways in brain cancer as well as the recent advances in understanding the nano-carrier approaches for enhancing drug delivery to the brain in the treatment of brain cancer.
... On the other hand, fluoxetine and indomethacin attenuated M1 macrophages but had no effect on M2 macrophages. This effect by indomethacin has been reported in different tissues and diseases [42,43]. Altogether, this suggests that Gβγ-GRK2 inhibition exerts superior anti-inflammatory effects in OA by attenuating the proinflammatory M1 macrophages and promotes healing by increasing the anti-inflammatory M2 macrophages, in contrast to fluoxetine and indomethacin, which inhibit both M1 and M2 macrophages. ...
The G-protein-coupled receptor kinase 2 (GRK2) is an important regulator of inflammation and pathological macrophage phenotype in a variety of diseases. We hypothesize that Gβγ-GRK2 signaling promotes the early inflammatory response and chondrocyte loss in osteoarthritis (OA). Using the destabilization of the medial meniscus (DMM) model in 12-week-old male C57BL/6 mice, we determined the role of Gβγ-GRK2 signaling in synovitis, macrophage activation, and OA development. We achieved Gβγ-GRK2 inhibition at the time of DMM by administering the Gβγ inhibitor “gallein” and the GRK2 inhibitor “paroxetine” daily, starting from 2 days before DMM surgery, for a duration of 1 or 12 weeks. Synovial and cartilage structural changes were evaluated by histomorphometry, and molecular events and macrophage activation were examined. We studied the direct role of Gβγ-GRK2 in synovitis and macrophage activation in vitro using SW982 and THP1 cells. Continuous Gβγ-GRK2 inhibition initiated at the time of DMM attenuated OA development and decreased chondrocyte loss more effectively than delayed treatment. GRK2 expression and the M1 macrophage phenotype were elevated in the inflamed synovium, while early gallein and paroxetine treatment for 1 and 12 weeks following DMM resulted in their reduction and an upregulated M2 macrophage phenotype. In vitro experiments showed that Gβγ-GRK2 inhibition attenuated synoviocyte inflammation and the M1 phenotype. We show that early Gβγ-GRK2 inhibition is of higher therapeutic efficacy in OA than delayed inhibition, as it prevents OA development by inhibiting the early inflammatory response.
... The neuroinflammation and the role of inflammatory mediators, such as COX-2, are critical components in establishing an immunosuppressed microenvironment, thus fueling GBM proliferation, invasion, and maintenance of stemness features (41). COXIB enhanced the tumor-associatedmacrophage-mediated anti-tumor immune responses by increasing monocyte cytokine production (42). The COX-2 role in macrophage polarization was also analyzed after NS398 treatment of bone marrow-derived macrophages that increased the secreted levels of TNFa and reduced the IL-10 secretion (42). ...
... COXIB enhanced the tumor-associatedmacrophage-mediated anti-tumor immune responses by increasing monocyte cytokine production (42). The COX-2 role in macrophage polarization was also analyzed after NS398 treatment of bone marrow-derived macrophages that increased the secreted levels of TNFa and reduced the IL-10 secretion (42). Our present findings show that EV released by TMZ-treated T98G shuttled COX-2 and, after effective internalization by U937 macrophage cells, induced a higher level of TGF-b1, a hallmark of the transition in M2 macrophage state (43). ...
Temozolomide (TMZ) resistance is frequent in patients with glioblastoma (GBM), a tumor characterized by a marked inflammatory microenvironment. Recently, we reported that cyclooxygenase-2 (COX-2) is upregulated in TMZ-resistant GBM cells treated with high TMZ concentrations. Moreover, COX-2 activity inhibition significantly counteracted TMZ-resistance of GBM cells. Extracellular vesicles (EV) are considered crucial mediators in orchestrating GBM drug resistance by modulating the tumor microenvironment (TME) and affecting the surrounding recipient cell phenotype and behavior. This work aimed to verify whether TMZ, at low and clinically relevant doses (5-20 µM), could induce COX-2 overexpression in GBM cells (T98G and U87MG) and explore if secreted EV shuttled COX-2 to recipient cells. The effect of COX-2 inhibitors (COXIB), Celecoxib (CXB), or NS398, alone or TMZ-combined, was also investigated. Our results indicated that TMZ at clinically relevant doses upregulated COX-2 in GBM cells. COXIB treatment significantly counteracted TMZ-induced COX-2 expression, confirming the crucial role of the COX-2/PGE2 system in TMZ-resistance. The COXIB specificity was verified on U251MG, COX-2 null GBM cells. Western blotting of GBM-EV cells showed the COX-2 presence, with the same intracellular trend, increasing in EV derived from TMZ-treated cells and decreasing in those derived from COXIB+TMZ-treated cells. We then evaluated the effect of EV secreted by TMZ-treated cells on U937 and U251MG, used as recipient cells. In human macrophage cell line U937, the internalization of EV derived by TMZ-T98G cells led to a shift versus a pro-tumor M2-like phenotype. On the other hand, EV from TMZ-T98G induced a significant decrease in TMZ sensitivity in U251MG cells. Overall, our results, in confirming the crucial role played by COX-2 in TMZ-resistance, provide the first evidence of the presence and effective functional transfer of this enzyme through EV derived from GBM cells, with multiple potential consequences at the level of TME.
... COX2 inhibitors, histone deacetylase (HDAC) inhibitors, phosphoinositide 3-kinase γ (PI3Kγ) inhibitors, and stimulator of interferon genes (STING) agonists are also used to reprogram TAMs. COX2 inhibition increases TNF-α, IL-12, and iNOS expression, shifting the macrophages to an antitumor phenotype (222,223). In a phase I clinical trial for the treatment of docetaxel-resistant prostate cancer, patients treated with a COX2 inhibitor (celecoxib) and an epidermal growth factor receptor inhibitor (gefitinib) showed reduced tumor growth and invasion (224). ...
Chronic inflammation increases the risk of several cancers, including gastric, colon, and hepatic cancers. Conversely, tumors, similar to tissue injury, trigger an inflammatory response coordinated by the innate immune system. Cellular and molecular mediators of inflammation modulate tumor growth directly and by influencing the adaptive immune response. Depending on the balance of immune cell types and signals within the tumor microenvironment, inflammation can support or restrain the tumor. Adding to the complexity, research from the past two decades has revealed that innate immune cells are highly heterogeneous and plastic, with variable phenotypes depending on tumor type, stage, and treatment. The field is now on the cusp of being able to harness this wealth of data to ( a) classify tumors on the basis of their immune makeup, with implications for prognosis, treatment choice, and clinical outcome, and ( b) design therapeutic strategies that activate antitumor immune responses by targeting innate immune cells.
Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... In part, this check may be anti-inflammatory. Consistent with prior reports, [6][7][8] we observed an increased LPS-dependent expression of inflammatory cytokines in Cox2 MKO macrophages. 5 However, macrophage COX2 may also modulate inflammation resolution. ...
... Chronic COX2 inhibition biases macrophage phenotype toward an inflammatory M1 state. 7,8 Inflammatory M1 macrophages exhibit less efferocytosis capacity than either M0 or M2c macrophages. 20 We thus considered the possibility that chronic or constitutive COX2 loss impairs macrophage efferocytosis by biasing macrophage phenotype during differentiation or polarization. ...
... 20 Likewise, there is evidence that COX2 can modulate macrophage polarization phenotype, thereby modulating efferocytosis capacity. 7,8,[52][53][54] Altogether, these reports indicate that COX2 activity during both differentiation and polarization can potentiate alternatively activated phenotypes and that the COX2 loss can promote classical activation. Consistent with these reports, we detected COX2dependent prostanoids during the differentiation of BMDMs (Figure 7). ...
Background and Aims
Phagocytosis (efferocytosis) of apoptotic neutrophils by macrophages anchors the resolution of intestinal inflammation. Efferocytosis prevents secondary necrosis and inhibits further inflammation, and also reprograms macrophages to facilitate tissue repair and promote resolution function. Macrophage efferocytosis and efferocytosis-dependent reprogramming are implicated in the pathogenesis of inflammatory bowel disease (IBD). We previously reported that absence of macrophage cyclooxygenase 2 (COX2) exacerbates IBD-like intestinal inflammation. To elucidate the underlying pathogenic mechanism, we investigated here whether COX2 mediates macrophage efferocytosis and efferocytosis-dependent reprogramming, including intestinal epithelial repair capacity.
Methods
Using apoptotic neutrophils and synthetic apoptotic targets, we determined the effects of macrophage specific Cox2 knockout and pharmacological COX2 inhibition on the efferocytosis capacity of mouse primary macrophages. COX2-mediated efferocytosis-dependent eicosanoid lipidomics were determined by LC-MS/MS. Small intestinal epithelial organoids were employed to assay the effects of COX2 on efferocytosis-dependent intestinal epithelial repair.
Results
Loss of COX2 impaired efferocytosis in mouse primary macrophages, in part, by affecting the binding capacity of macrophages for apoptotic cells. This effect was comparable to that of high dose lipopolysaccharide (LPS) and was accompanied by both dysregulation of macrophage polarization and the inhibited expression of genes involved in apoptotic cell binding. COX2 modulated the production of efferocytosis-dependent lipid inflammatory mediators that include the eicosanoids PGI2, PGE2, LXA4 and 15d-PGJ2; and further affected secondary efferocytosis. Finally, macrophage efferocytosis induced, in a macrophage COX2 dependent manner, a tissue restitution and repair phenotype in intestinal epithelial organoids.
Conclusions
Macrophage COX2 potentiates efferocytosis capacity and efferocytosis-dependent reprogramming, facilitating macrophage intestinal epithelial repair capacity.
... Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), is mainly used for treatment of pain, inflammation, and fever in several chronic inflammatory diseases (Eccleston et al., 2017;Nalamachu & Wortmann, 2014). In terms of neuroinflammation, indomethacin and other NSAIDs have been reported to have different effects on LPS-induced microglia activation and pro-inflammatory molecule expression; that is, inhibition, no effect and augmentation of LPS-induced neuroinflammatory effects (Aid, Langenbach & Bosetti, 2008;Banks et al., 2015;Blais, Turrin & Rivest, 2005;Na et al., 2015;Nakamori et al., 1994;Sacco et al., 1998;Teeling et al., 2007). ...
... The difference between the effects of indomethacin on LPS-induced elevation in Nos2 transcripts in the current study and that of DiGirolamo and colleagues (Di Girolamo et al., 2003) could be due the difference in animal species used that is, mice versus rats or the number of doses that is, three doses over three days compared to a single dose. Repeated or chronic administration of indomethacin has been shown to cause microglia activation or enhance LPS-induced inflammation (Na et al., 2015;Prechel et al., 2000). Various studies investigating the role of NSAIDs in treating neurodegenerative diseases have produced conflicting results. ...
Indomethacin and other non-steroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain and fever including during infections. However, some studies suggest that NSAIDs protect against neuroinflammation, while some find no effects or worsening of neuroinflammation. We evaluated the effect of indomethacin alone on in combination with minocycline, a drug that inhibits neuroinflammation, on the expression of transcripts of neuroinflammatory molecules-induced by lipopolysaccharide (LPS) in the brain of mice. Inoculation of male BALB/c mice with LPS induced the expression of the microglia marker ionized calcium binding adaptor molecule protein, mRNA expression of the genes for cytokines interleukin-1beta ( Il1b ) and tumor necrosis factor-alpha ( Tnf ) and inducible nitric oxide synthase gene ( Nos2 ), but not Il10 , in the brain. Treatment with indomethacin had no significant effect on the cytokines or Nos2 mRNA expression in naïve animals. However, pretreatment with indomethacin increased LPS-induced Nos2 mRNA and inducible nitric oxide (iNOS) protein expression, but had no significant effect on LPS-induced mRNA expression of the cytokines. Minocycline reduced LPS-induced Il1b and Tnf , but not Nos2 , mRNA expression. Treatment with indomethacin plus minocycline had no effect on LPS-induced Il1b, Tnf and Nos2 mRNA expression. In conclusion these results show that indomethacin significantly augments LPS-induced Nos2 mRNA and iNOS protein expression in the brain. In the presence of indomethacin, minocycline could not inhibit LPS-induced pro-inflammatory cytokine expression. Thus, indomethacin could exacerbate neuroinflammation by increasing the expression of iNOS and also block the anti-inflammatory effects of minocycline.
... At this dose, indomethacin did not attenuate the immune response at 7 d or 30 d. In fact, chronic long term COX inhibition in vivo resulted in systemic macrophage activation which drove greater inflammation after LPS challenge (Na et al. 2015). Furthermore, Caldwell et al. demonstrated that indomethacin delivered via osmotic pump in the peritoneal cavity at a dose of 25 µg h −1 for 14 d (vs. ...
Key points
Compared with sham rats, rats a week after acute lung injury (ALI) express more pro‐inflammatory cytokines in their brainstem respiratory control nuclei, exhibit a higher respiratory frequency (fR) and breathe with a more predictable pattern.
These characteristics of the respiratory pattern persist in in situ preparations even after minimizing pulmonary and chemo‐afferent inputs.
Interleukin (IL)‐1β microinjected in the nucleus tractus solitarii increases fR and the predictability of the ventilatory pattern similar to rats with ALI.
Intracerebroventricular infusion of indomethacin, an anti‐inflammatory drug, mitigates the effect of ALI on fR and ventilatory pattern variability.
We conclude that changes in the ventilatory pattern after ALI result not only from sensory input due to pulmonary damage and dysfunction but also from neuro‐inflammation.
Abstract
Acute lung injury (ALI) increases respiratory rate (fR) and ventilatory pattern variability (VPV), but also evokes peripheral and central inflammation. We hypothesized that central inflammation has a role in determining the ventilatory pattern after ALI. In rat pups, we intratracheally injected either bleomycin to induce ALI or saline as a sham control. One week later, we recorded the ventilatory pattern of the rat pups using flow‐through plethysmography, then formed in situ preparations from these pups and recorded their ‘fictive’ patterns from respiratory motor nerves. Compared with the ventilatory pattern of the sham rat pups, injured rat pups had increased fR and predictability. Surprisingly, the fictive patterns of the in situ preparations from ALI pups retained these characteristics despite removing their lungs to eliminate pulmonary sensory inputs and perfusing them with hyperoxic artificial cerebral spinal fluid to minimize peripheral chemoreceptor input. Histological processing revealed increased immunoreactivity of the pro‐inflammatory cytokine Interleukin‐1β (IL‐1β) in the nucleus tractus solitarii (nTS) from ALI but not sham rats. In subsequent experiments, we microinjected IL‐1β in the nTS bilaterally in anaesthetized naïve adult rats, which increased fR and predictability of ventilatory pattern variability (VPV) after 2 h. Finally, we infused indomethacin intracerebroventricularly during the week of survival after ALI. This did not affect sham rats, but mitigated changes in fR and VPV in ALI rats. We conclude that neuro‐inflammation has an essential role in determining the ventilatory pattern of ALI rats.
... The most straightforward method is inducing or repolarizing TAMs towards the M1-like phenotype in tumor stroma. The re-polarization of M2-like TAMs can be done through various means such as by using a; (a)TLR agonist, M1-stimulating agents and cytokines, (C)by application of antagonistic antibodies to shut down M2-related pathways to further force macrophages to adopt pro-inflammatory M1 phenotype, (d) by employing antisense miRNA (e.g., miR-155 and miR-125) to inhibit M2-related pathways or (e) by using small inhibiting molecules (e.g., COX2 (cyclooxygenase) inhibitor, histone deacetylase (HDAC) inhibitor, etc.) [130,132,[134][135][136][137]. ...
Background
This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating macrophages in alternatively activated anti-inflammatory pro-tumorigenic M2 macrophage phenotypes and classically activated pro-inflammatory, anti-tumorigenic M1 macrophage phenotypes in the tumor microenvironment (TME). The review is divided into two main parts, as follows: (1) role of exosomes in alternatively activating M2-like macrophages-breast cancer-derived exosomes, hepatocellular carcinoma (HCC) cell-derived exosomes, lung cancer-derived exosomes, prostate cancer-derived exosomes, Oral squamous cell carcinoma (OSCC)—derived exosomes, epithelial ovarian cancer (EOC)—derived exosomes, Glioblastoma (GBM) cell-derived exosomes, and colorectal cancer-derived exosomes, (2) role of exosomes in classically activating M1-like macrophages, oral squamous cell carcinoma-derived exosomes, breast cancer-derived exosomes, Pancreatic-cancer derived modified exosomes, and colorectal cancer-derived exosomes, and (3) exosomes and antibody-dependent cellular cytotoxicity (ADCC). This review addresses the following subjects: (1) crosstalk between cancer-derived exosomes and recipient macrophages, (2) the role of cancer-derived exosome payload(s) in modulating macrophage fate of differentiation, and (3) intracellular signaling mechanisms in macrophages regarding the exosome’s payload(s) upon its uptake and regulation of the TME.EvidenceUnder the electron microscope, nanoscale exosomes appear as specialized membranous vesicles that emerge from the endocytic cellular compartments. Exosomes harbor proteins, growth factors, cytokines, lipids, miRNA, mRNA, and DNAs. Exosomes are released by many cell types, including reticulocytes, dendritic cells, B-lymphocytes, platelets, mast cells, and tumor cells. It is becoming clear that exosomes can impinge upon signal transduction pathways, serve as a mediator of signaling crosstalk, thereby regulating cell-to-cell wireless communications.Conclusion
Based on the vesicular cargo, the molecular constituents, the exosomes have the potential to change the fate of macrophage phenotypes, either M1, classically activated macrophages, or M2, alternatively activated macrophages. In this review, we discuss and describe the ability of tumor-derived exosomes in the mechanism of macrophage activation and polarization.
... However, NSAIDs like ibuprofen, diclofenac, naproxen sodium, and acetylsalicylic acid that act through cyclooxygenase-1 and 2 inhibition have a controversial role in macrophage function, especially if administered chronically [13][14][15]. In addition, macrophages display a spectrum of diverse phenotypes depending on environmental conditions like chronic inflammation [16]. ...
Background: It has been suggested that the function of myeloid immune cells, especially macrophages in schizophrenia patients (SCZ), is impaired. Considering the role of macrophages in induction of inflammatory responses, the purpose of this study is to examine the response of monocyte-derived macrophages (MDM) of schizophrenia patients to Toxoplasma gondii (T. gondii) challenge. Materials and Methods: MDMs were generated from 20 SCZ and 10 healthy controls (HC). The cells were exposed to T. gondii. The Cytokine (IL-10, IL-12, IL-6, and TNF-α) and nitric oxide (NO) productions were measured. The expression of miR146a and miR155 was examined using qPCR. Results: The level of NO was significantly higher in the supernatant of MDMs of SCZ compared with the HC (P≤0.05) in response to T. gondii. There was no difference in cytokine (IL-10, IL-12, IL-6, and TNF-α) production of SCZ compared to the controls. The effect of miR-155/ miR-146a on inflammatory cytokine production was confirmed using anti-miRNAs. There were no significant effect in miR-155/ miR-146a expression of macrophages of schizophrenia patients to T. gondii compared to control. Conclusion: In this study, although the cytokine response and the amount of miR-155/ miR-146a expression of macrophages to T. gondii was not significantly different between the schizophrenia patients and the healthy subjects, the significant differences in the production of nitric oxide strengthen the hypothesis of the functional failure of these cells.
... Blocks PI3K/Akt COX2 inhibitor is approved for leukemia (81) mentioned, we summarize the common polarization targets in Table 1. Here, we describe some specific studies that have been performed regarding TAM depolarization. ...
With the development of nanotechnology, significant progress has been made in the design, and manufacture of nanoparticles (NPs) for use in clinical treatments. Recent increases in our understanding of the central role of macrophages in the context of inflammation and cancer have reinvigorated interest in macrophages as drug targets. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in cancer and inflammation processes. Thus, NPs tailored to accurately target macrophages have the potential to transform disease treatment. Herein, we first present a brief background information of NPs as drug carriers, including but not limited to the types of nanomaterials, their biological properties and their advantages in clinical application. Then, macrophage effector mechanisms and recent NPs-based strategies aimed at targeting macrophages by eliminating or re-educating macrophages in inflammation and cancer are summarized. Additionally, the development of nanocarriers targeting macrophages for disease diagnosis is also discussed. Finally, the significance of macrophage-targeting nanomedicine is highlighted, with the goal of facilitating future clinical translation.
