Macrophages are critical mediators of the innate immune response against foreign pathogens, including bacteria, physical stress, and injury. Therefore, these cells play a key role in the ..."inflammatory pathway" which in turn can lead to an array of diseases and disorders such as autoimmune neuropathies and myocarditis, inflammatory bowel disease, atherosclerosis, sepsis, arthritis, diabetes, and angiogenesis. Recently, more studies have focused on the macrophages inflammatory diseases since the discovery of the two subtypes of macrophages, which are differentiated on the basis of their phenotype and distinct gene expression pattern. Of these, M1 macrophages are pro-inflammatory and responsible for inflammatory signaling, while M2 are anti-inflammatory macrophages that participate in the resolution of the inflammatory process, M2 macrophages produce anti-inflammatory cytokines, thereby contributing to tissue healing. Many studies have shown the role of these two subtypes in the inflammatory pathway, and their emergence appears to decide the fate of inflammatory signaling and disease progression. As a next step in directing the pro-inflammatory response toward the anti-inflammatory type after an insult by a foreign pathogen (e. g., bacterial lipopolysaccharide), investigators have identified many natural compounds that have the potential to modulate M1 to M2 macrophages. In this review, we provide a focused discussion of advances in the identification of natural therapeutic molecules with anti-inflammatory properties that modulate the phenotype of macrophages from M1 to M2.
P2X7 receptors are ATP‐gated cation channels; their activation in macrophage also leads to rapid opening of a membrane pore permeable to dyes such as ethidium, and to release of the pro‐inflammatory ...cytokine, interleukin‐1β (IL‐1β). It has not been known what this dye‐uptake path is, or whether it is involved in downstream signalling to IL‐1β release. Here, we identify pannexin‐1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, as this dye‐uptake pathway and show that signalling through pannexin‐1 is required for processing of caspase‐1 and release of mature IL‐1β induced by P2X7 receptor activation.
Inflammation mediated by both innate and adaptive immune cells is necessary for several important processes during pregnancy. Pro-inflammatory immune cell activation plays a critical role in embryo ...implantation, placentation, and parturition; however dysregulation of these cells can lead to detrimental pregnancy outcomes including spontaneous abortion, fetal growth restriction, maternal pathology including hypertensive disorders, or fetal and maternal death. The resolution of inflammation plays an important role throughout pregnancy and is largely mediated by immune cells that produce interleukin (IL)-4 and IL-10. The temporal and spatial aspects of reducing inflammation during pregnancy represent a complex process that if not functioning optimally can lead to persistent inflammation and pregnancy complications. In this review, we examine how immune cells that produce IL-4 and IL-10 are regulated throughout pregnancy as well as the effects that reduced IL-4 and IL-10 signaling has on fetal and maternal physiology.
Oligodendrocyte progenitor cells (OPCs) were regarded for years solely for their regenerative role; however, their immune‐modulatory roles have gained much attention recently, particularly in the ...context of multiple sclerosis (MS). Despite extensive studies on OPCs, there are limited data elucidating the interactions between their intrinsic regenerative and immune functions, as well as their relationship with the inflamed central nervous system (CNS) environment, a key factor in MS pathology. We examined the effects of pro‐inflammatory cytokines, represented by interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α, as well as anti‐inflammatory cytokines, represented by interleukin (IL)‐4 and IL‐10, on OPC differentiation and immune characteristics. Using primary cultures, enzyme‐linked immunosorbent assay and immunofluorescence stainings, we assessed differentiation capacity, phagocytic activity, major histocompatibility complex (MHC)‐II expression, and cytokine secretion. We observed that the anti‐inflammatory milieu (IL4 and IL10) reduced both OPC differentiation and immune functions. Conversely, exposure to TNF‐α led to intact differentiation, increased phagocytic activity, high levels of MHC‐II expression, and cytokines secretion. Those effects were attributed to signalling via TNF‐receptor‐2 and counteracted the detrimental effects of IFN‐γ on OPC differentiation. Our findings suggest that a pro‐regenerative, permissive inflammatory environment is needed for OPCs to execute both regenerative and immune‐modulatory functions.
Anti‐inflammatory milieu (IL4 and IL10) reduced both OPC differentiation and immune functions. Conversely, exposure to TNF‐α led to intact differentiation, increased phagocytic activity, high levels of MHC‐II expression, cytokines secretion, and lower levels of morphological complexity. Those effects were attributed to signalling via TNFR2 and counteracted the detrimental effects of IFNγ on OPC differentiation. Our findings point towards the essentiality of a pro‐regenerative inflammatory environment, emphasising the pivotal role of TNFα and TNFR2 in harmonising the balance between the regenerative and immunological tasks of OPCs in the inflamed CNS.
The optimal treatment for complex fractures and large bone defects is an important unsolved issue in orthopedics and related specialties. Approximately 5-10% of fractures fail to heal and develop ...non-unions. Bone healing can be characterized by three partially overlapping phases: the inflammatory phase, the repair phase, and the remodeling phase. Eventual healing is highly dependent on the initial inflammatory phase, which is affected by both the local and systemic responses to the injurious stimulus. Furthermore, immune cells and mesenchymal stromal cells (MSCs) participate in critical inter-cellular communication or crosstalk to modulate bone healing. Deficiencies in this inter-cellular exchange, inhibition of the natural processes of acute inflammation, and its resolution, or chronic inflammation due to a persistent adverse stimulus can lead to impaired fracture healing. Thus, an initial and optimal transient stage of acute inflammation is one of the key factors for successful, robust bone healing. Recent studies demonstrated the therapeutic potential of immunomodulation for bone healing by the preconditioning of MSCs to empower their immunosuppressive properties. Preconditioned MSCs (also known as "primed/ licensed/ activated" MSCs) are cultured first with pro-inflammatory cytokines (e.g., TNFα and IL17A) or exposed to hypoxic conditions to mimic the inflammatory environment prior to their intended application. Another approach of immunomodulation for bone healing is the resolution of inflammation with anti-inflammatory cytokines such as IL4, IL10, and IL13. In this review, we summarize the principles of inflammation and bone healing and provide an update on cellular interactions and immunomodulation for optimal bone healing.
Leucine-rich α-2-glycoprotein-1 (LRG) has been found to participate in the development of various cancers through its involvement in TGF-β1-induced epithelial-mesenchymal transition (EMT) and/or ...angiogenesis and can be induced by inflammatory cytokines, such as IL-6. As we previously showed the implication of IL-6/TGF-β axis in EMT of cholangiocarcinoma cells, we herein explored the prognostic impact of LRG in postoperative intrahepatic cholangiocarcinoma (ICC) and assessed the association between tumor LRG and factors such as TGF-β1, IL-6, and the tumor microvessel density.
We determined the expression of LRG, IL-6, TGF-β1, and CD31 in cancer tissues from 50 ICC patients by immunohistochemistry and analyzed their association with the prognosis.
The LRG expression was closely associated with recurrence-free survival (RFS) and overall survival (OS) in postoperative ICC. A multivariate Cox regression model indicated that LRG as an independently associated with poor RFS (hazard ratio = 2.4339, P = 0.0354) and OS (hazard ratio = 2.8892, P = 0.0268). The LRG expression was significantly associated with the expression of TGF-β1 (P = 0.0003) and IL-6 (P = 0.0164).
The upregulation of LRG in tumors was an independent prognostic factor in patients with postoperative ICC. LRG was closely associated with the TGF-β1 expression and seems to be an important member of the IL-6/TGF-β1 axis.
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease of unknown etiology. It is characterized by the presence of rheumatoid factor and anti-citrullinated peptide antibodies. ...Initial phase of RA involves the activation of both T and B cells. Cytokines have a crucial role in the pathophysiology of RA as pro-inflammatory cytokines such as TNFα, IL-1, IL-17 stimulates inflammation and degradation of bone and cartilage. There occurs an imbalance between the pro- and anti-inflammatory cytokine activities which leads to multisystem immune complications. There occurs a decline in the number of Treg cells which may also play an important role in pathophysiology of the disease. In RA patients, serum or plasma level of cytokines may indicate the severity of disease. Cytokine gene polymorphism could be used as markers of susceptibility and severity of RA. Anti-cytokine agents seem to emerge as potent drug molecules to treat RA. Many clinical trials are ongoing and several positive results have been obtained. There is a need to develop potential anti-cytokine agents that target numerous pathways involved in the pathogenesis of RA. This review article describes the effector functions of pro- and anti-inflammatory cytokines and the role of cytokine gene polymorphism in the pathogenesis of RA. Anti-cytokine agents that are currently available and those that are still in clinical trials have also been summarized.
•Rheumatoid arthritis is an autoimmune, inflammatory and multisystem disorder which is characterised by the inflammation of synovial membrane.•Predominance of pro-inflammatory cytokines over anti-inflammatory cytokines occurs.•Role of various pro and anti-inflammatory cytokines in the pathogenesis of rheumatoid arthritis have been discussed.•Cytokine gene polymorphism could be used as markers of susceptibility and severity of RA.•Anti-cytokine agents that are currently available and those that are still in clinical trials have also been summarized.
Objective: To investigate wound healing, antimicrobial and antioxidant activity of leaf extract of Pongamia Pinnata. Materials and methods: Methanolic extracts of P. pinnata leaf were studied for ...wound healing efficiency, and was assessed by the rate of wound contraction, tensile strength, breaking strength, hydroxyproline and hexosamine content, along with its effect on pro-inflammatory and anti-inflammatory cytokines was assessed using excision and incision model of wound repair in Wistar rats. Antimicrobial activity against ten microorganisms was also assessed. In vivo antioxidant activity was performed to understand the mechanism of wound healing potency. Results: The results indicated that P. pinnata extract has potent wound healing capacity as evident from the wound contraction and increased tensile strength. Hydroxyproline and hexosamine expression were also well correlated with the healing pattern observed. extract exhibited significant antimicrobial activity, Staphylococcus aureus, Staphylococcus pyogenes, Staphylococcus epidermidis, Escherichia coli, Micrococcus luteus, Enterobacter aerogenes, Salmonella typhi, Pseudomonas aeruginosa, Candida albicans, Aspergillus niger also indicate that P. pinnata posses potent antioxidant activity by inhibition lipid per-oxidation, reduce glutathione, superoxide dismutase level and increases catalase activity. During early wound healing phase TNF-α and IL-6 level were found to be up-regulated by P. pinnata treatment. Conclusion: Increased wound contraction and tensile strength, augmented hydroxyproline and hexosamine content, antioxidative activity and moderate antimicrobial activity support the early wound healing exhibited by P. pinnata. Induction in cytokine production may be one of the mechanisms in accelerating the wound healing. Results suggest that P. pinnata may be useful in tropical management of wound healing.
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