Intravesicular administration of sodium hyaluronate ameliorates the inflammation and cell proliferation of cystitis cystica et glandularis involving interleukin-6/JAK2/Stat3 signaling pathway

Abstract

Cystitis cystica et glandularis (CCEG) is a chronic cystitis that causes extreme agony in affected patients. However, there are lack of effective conservative treatments. In this study, it is evident that intravesicular sodium hyaluronate (SH) therapy significantly improved the clinical symptoms of CCEG patients and ameliorated the bladder mucosal inflammation and cell proliferation characteristics of the disease. Immunohistochemical staining showed that the staining intensities of hyaluronidase (HYAL 1/2), CD44, IL-6 and phosphorylated signal transducer and activator of transcription 3 (p-Stat3) in bladder mucosal tissue were significantly increased in CCEG patients compared with control patients and that intravesicular SH treatment suppressed these protein expression. We established a CCEG rat model by treating rats with E. coli intravesicularly, and we found that HYAL 1/2 and CD44 expression levels were significantly increased in the E. coli group compared with the NC group. Activation of the IL-6/JAK2/Stat3 pathway and the expression levels of the downstream pro-apoptotic proteins Mcl-1 and Bcl-xL were also significantly increased in the E. coli group compared with the NC group. The above changes were significantly mitigated by intravesicular SH treatment. Therefore, SH may serve as an effective therapy for CCEG by inhibiting bladder mucosal inflammation and proliferation.

IL-38 has an anti-inflammatory action in psoriasis and its expression correlates with disease severity and therapeutic response to anti-IL-17A treatment

“…3a ). Other than inducing the expression of chemokines attracting neutrophils and T cells, IL-36 cytokines interfere with keratinocyte differentiation in organotypic models by downregulating filaggrin 8 , 13 . We thus analyzed the effects of IL-38 on differentiation and inflammatory responses induced by IL-36γ in keratinocytes.…”

“…In support of this hypothesis, our results show that keratinocytes undergoing terminal differentiation release higher levels of IL-38 compared with IL-36Ra. However, IL-17, IL-22, and IL-36γ, known to inhibit the terminal keratinocyte differentiation 8 , 20 , have inhibitory effects on IL-38 expression, although they induce IL-36Ra antagonist. A predictive analysis of potential transcriptional factor-binding sites on IL-38 and IL-36Ra promoter sequences revealed the presence in the promoter of IL-38, but not of IL-36Ra, of elements likely binding to cAMP-responsive repressors, such as E4BP4 and ICER, and Kruppel-like factors, known to be induced by inflammatory cytokines and related to keratinocyte differentiation 35 – 37 .…”

“…IL-36 agonists are strongly expressed in psoriatic skin of individuals affected by plaque psoriasis and generalized pustular psoriasis. Here, these cytokines have inflammatory effects on many cell targets, mainly keratinocytes, by interfering with their cornification programs and inducing the release of antimicrobial peptides and chemokines active on neutrophils and Th17 lymphocytes 8 . IL-36s also promote proliferation and migration of human dermal microvascular endothelial cell (HDMEC), thus contributing to the dermal capillary dilatation typical of psoriatic lesions 9 .…”

Role of the Janus kinase 2/signal transducers and activators of transcription 3 pathway in the protective effect of remote ischemia preconditioning against cerebral ischemia–reperfusion injury in rats

“…RIPC was carried out as described previously 10. First, the operator anesthetized the rats with 1% pentobarbital sodium salt (90 mg/kg) by an intraperitoneal injection.…”

“…The cells were analyzed by fluorescence microscopy. TUNEL-positive cells with blue-stained apoptotic bodies were considered apoptotic cells 10. An examiner blinded to the experimental groups selected six high-power regions in the infarct area of each rat brain slice for evaluation under a microscope at a magnification of ×200.…”