IL-4 and serum amyloid P inversely regulate fibrocyte differentiation by targeting store-operated Ca 2+ channels

Abstract

IL-4 and SAP reversely regulates cultured fibrocytes differentiation in vitro by respectively promoting or inhibiting the expression and activity of SOC channels in fibrocytes.

Fibrocytes, Wound Healing, and Corneal Fibrosis

“…27 Fibrocytes also express the chemokine receptors CCR2, CCR3, CCR5, CCR7, CXCR4, CXCR6, and CX3CR1, host defense Fc receptors for immunoglobulin G (CD32 and CD64), antigen presentation and costimulatory molecules of lymphocyte activation (major histocompatibility complex [MHC] class I and II/CD80 and CD86), and cell surface enzymes (CD10 and CD13). 24,25,27,[36][37][38] The complete list of fibrocytes markers is presented in Table 1. 8,24,25,39 In the majority of studies reported, fibrocytes were identified by a combination of expressed markers, for example, the simultaneous expression of CD34 or CD45 or CD11b and collagen type I or collagen type III.…”

“…13,45,46 Niedermeier et al 26 suggest that the interaction between Th2 cytokines and fibrocytes precursor cells occurs via a mTOR-PI3 kinase dependent pathway. Zhong et al 36 demonstrate that IL-4 facilitates the in vitro differentiation of fibrocytes by increasing the activity and expression of store-operated Ca 2+ entry (SOCE) channels. In their studies, blockage of SOCE channels with SKF-96365 significantly inhibits IL-4induced differentiation of fibrocytes.…”

“…In their studies, blockage of SOCE channels with SKF-96365 significantly inhibits IL-4induced differentiation of fibrocytes. 36 Yan et al 47 show that Th2 cytokines induce the JAK3/STAT6 signaling pathway and stimulate bone marrow-derived fibroblast activation, which has been shown to play a role in the development of interstitial renal fibrosis. These authors further confirm the role of STAT6 signaling in myeloid fibroblast activation by using CP690550 (a JAK3-specific inhibitor) and STAT6 deficiency in bone marrow chimeric experiments.…”

“…53 In spite of SAP injections having markedly reduced the number of proliferative fibrocytes, and preventing fibrosis, SAP has not been shown to suppress inflammation or chemokine expression. 15 Zhong et al 36 clarify the mechanism of action of SAP and demonstrate that SAP inhibits IL-4-induced differentiation of fibrocytes due to its SAP inhibiting effect on SOCE channels.…”

Ca2+ signalling in fibroblasts and the therapeutic potential of KCa3.1 channel blockers in fibrotic diseases

“…In addition, knock‐down of Orai1 channels inhibited TGF‐β1‐induced epithelial–mesenchymal transition, [Ca 2+ ] i influx and phosphorylation of SMAD2/3 (Mai et al, ). Peripheral blood monocyte‐derived IL‐4‐dependent fibrocyte differentiation was dependent on store‐operated Ca 2+ channels and increased the expression of both STIM1 and Orai1 (Zhong et al, ). Therefore, targeting these channels in fibrosis might reduce trafficking of circulating fibrocytes into fibrosing organs such as the lung in IPF, where increased circulating fibrocytes are an indicator of disease activity and a predictor of early mortality (Moeller et al, ; Wright et al, ).…”