Role Of Mast Cells In Inflammation Research Articles

Morphological characterization of Mast cells in the cochlea during postnatal rodent development

Mast cells (MC) are immune cells of hematopoietic origin widely distributed in the mammalian body's connective tissue. Their activity plays a potential immunoregulatory role associated with allergic reactions, autoimmune, cardiovascular, and neuronal diseases. Previously, the inner ear‐related MCs were described in the endolymphatic sac. However, the presence of MCs in the mammalian cochlea was not yet investigated.Here, we demonstrate for the first time that the MCs are present in the healthy cochlea of C57BL/6 mice and Wistar rats. Using histochemistry and immunohistochemistry on the cryo‐/paraffine sections of the whole cochlea and cochlea explants, we detected MCs in the modiolus, spiral ligament, scala vestibuli, and occasionally in scala tympani. The identified MCs expressed various MC‐specific markers: cKit/CD117, chymase, tryptase, and FcεRIa. Quantitative analysis demonstrated a significant decrease in the number of MCs during the postnatal development, resulting in only a few MCs present in the cochlea of rats and mice. In addition, 24h incubation of the cochlear explant with 40 µM of cisplatin lead to a significant reduction of MC numbers.The presence of MCs in the cochlea may shed new light on postnatal maturation of the auditory periphery and possible involvement in cisplatin ototoxicity. Currently, our findings expand the knowledge about the physiology and pathology of the auditory periphery.Considering the pivotal role of MCs in inflammation, future functional studies should explain this new basic knowledge and translate it into clinical application.

The RLR/NLR expression and pro-inflammatory activity of tissue mast cells are regulated by cathelicidin LL-37 and defensin hBD-2

Considering the significance of mast cells (MCs) in the course of various physiological and pathological processes, and the pivotal role of endogenous molecules, i.e., cathelicidins and defensins as multifunctional modulators, the study examines the constitutive and cathelicidin LL-37/defensin hBD-2-induced expression of certain NLRs and RLRs, i.e., NOD1, NOD2, and RIG-I, in fully-mature tissue MCs, and the impact of LL-37 and hBD-2 on MC pro-inflammatory activity. All experiments were carried out in vitro on freshly-isolated peritoneal (P)MCs. qRT-PCR, western blotting, flow cytometry, and confocal microscopy were used to evaluate both constitutive and LL-37/hBD-2-induced expression of NOD1, NOD2, and RIG-I receptors. ROS was determined using H2DCFDA, and Boyden microchamber assay was used to define the migratory response. Standard techniques assessed histamine, cysLT, and chemokine generation. PMCs express NOD1, NOD2, and RIG-I constitutively. LL-37 and hBD-2 enhance the expression and induce translocation of the studied receptors and directly activate the pro-inflammatory and migratory responses of PMCs. Observations demonstrate that LL-37 and hBD-2 might augment MC capability and sensitivity to NLR and RLR ligands and strengthen the role of MCs in inflammation.

Critical role of inflammatory mast cell in fibrosis: Potential therapeutic effect of IL-37.

Fibrosis involves the activation of inflammatory cells, leading to a decrease in physiological function of the affected organ or tissue. To update and synthesize relevant information concerning fibrosis into a new hypothesis to explain the pathogenesis of fibrosis and propose potential novel therapeutic approaches. Literature was reviewed and relevant information is discussed in the context of the pathogenesis of fibrosis. A number of cytokines and their mRNA are involved in the circulatory system and in organs of patients with fibrotic tissues. The profibrotic cytokines are generated by several activated immune cells, including fibroblasts and mast cells (MCs), which are important for tissue inflammatory responses to different types of injury. MC-derived TNF, IL-1, and IL-33 contribute crucially to the initiation of a cascade of the host defence mechanism(s), leading to the fibrosis process. Inhibition of TNF and inflammatory cytokines may slow the progression of fibrosis and improve the pathological status of the affected subject. IL-37 is generated by various types of immune cells and is an IL-1 family member protein. IL-37 is not a receptor antagonist; it binds IL-18 receptor alpha (IL-18Rα) and delivers the inhibitory signal by using TIR8. It has been shown that IL-37 can be protective in inflammation and injury, and inhibits both innate and adaptive immunity. IL-37 may be useful for suppression of inflammatory diseases induced by inhibiting MyD88-dependent TLR signalling. In addition, IL-37 downregulates NF-κB induced by TLR2 or TLR4 through a mechanism dependent on IL-18Rα. This review summarizes current knowledge on the role of MC in inflammation and tissue/organ fibrosis, with a focus on the therapeutic potential of IL-37-targeting cytokines.