Adiponectin induces interleukin-6 production and its underlying mechanism in adult rat cardiac fibroblasts.

It has been reported that adiponectin enhances interleukin-6 (IL-6) production in cardiac fibroblasts derived from neonatal rats and adult mice, but the mechanisms involved remain unknown. In the present study, we explored the effect and mechanisms of adiponectin on IL-6 production in adult rat cardiac fibroblasts. Globular adiponectin (gAd) increased IL-6 mRNA expression and protein secretion in cultured adult rat cardiac fibroblasts. gAd-induced IL-6 release was attenuated after RNA interference inhibition of adiponectin receptor 1 (AdipoR1), but not AdipoR2 or an adaptor protein APPL1. gAd increased the phosphorylation of AMP-activated protein kinase (AMPK), p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun-N-terminal kinase (JNK). Inhibitors of AMPK (araA), p38MAPK (SB202190), and ERK1/2 (PD98059 and U0126) but not JNK (SP600125) suppressed gAd-induced IL-6 production. In transient transfection assays of IL-6 promoter/luciferase reporter plasmids, gAd increased the transcriptional activity of the full-length IL-6 promoter. Deletion analysis of the IL-6 promoter indicated that activator protein-1 (AP-1), nuclear factor for IL-6 (NF-IL-6) and nuclear factor κB (NF-κB) binding sites were important for gAd-induced IL-6 transcription. Our data suggest that gAd enhances IL-6 synthesis and release in adult rat cardiac fibroblasts through AdipoR1. Activation of AMPK, p38MAPK, and ERK1/2 mediates the intracellular signal transduction. AP-1, NF-IL-6, and NF-κB cis-elements are required for gAd-induced IL-6 transcription.

Fan D ，Li L ，Wang C ，Cui XB ，Zhou Y ，Wu LL ... -  《-》

Globular adiponectin activates nuclear factor-kappaB and activating protein-1 and enhances angiotensin II-induced proliferation in cardiac fibroblasts.

Hattori Y ，Hattori S ，Akimoto K ，Nishikimi T ，Suzuki K ，Matsuoka H ，Kasai K ... -  《DIABETES》

IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta , NF-kappaB, and AP-1 activation.

Cortez DM ，Feldman MD ，Mummidi S ，Valente AJ ，Steffensen B ，Vincenti M ，Barnes JL ，Chandrasekar B ... -  《AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY》

Interleukin-1beta induces ICAM-1 expression enhancing leukocyte adhesion in human rheumatoid arthritis synovial fibroblasts: involvement of ERK, JNK, AP-1, and NF-kappaB.

Yang CM ，Luo SF ，Hsieh HL ，Chi PL ，Lin CC ，Wu CC ，Hsiao LD ... -  《-》

IL-17R activation of human periodontal ligament fibroblasts induces IL-23 p19 production: Differential involvement of NF-κB versus JNK/AP-1 pathways.

Interleukin (IL)-23 is an essential cytokine involved in the expansion of a novel CD4(+) T helper subset known as Th17, which has been implicated in the pathogenesis of periodontitis recently. This study hypothesised that Th17 signature cytokine IL-17 may target specialised human periodontal ligament fibroblasts (hPDLFs) for production of IL-23 p19, a key subunit of IL-23. Primary hPDLFs had steady expression of IL-17 receptor (IL-17R) mRNA and surface-bound protein. IL-17 was capable of stimulating the expression of IL-23 p19 mRNA and protein in cultured hPDLFs, which was attenuated by IL-17 or IL-17R neutralising antibodies. In accordance with the enhanced expression of IL-23 p19, IL-17 stimulation resulted in rapid activation of Akt, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2, c-Jun-N-terminal kinase (JNK), nuclear factor-kappaB (NF-κB), and activator protein-1 (AP-1) in hPDLFs. Inhibitors of Akt, p38 MAPK, ERK 1/2, or NF-κB significantly suppressed, whereas blocking JNK and AP-1 substantially augmented IL-23 p19 production from IL-17-stimulated hPDLFs. Moreover, IL-17-initiated NF-κB activation was blocked by Akt, p38 MAPK, or ERK 1/2 inhibition, while AP-1 activity was specifically abrogated by JNK inhibition. Thus, these results provide evidence that hPDLFs are a target of Th17, and that IL-17 appears to up-regulate the expression of IL-23 p19 via a homeostatic mechanism involving Akt-, p38 MAPK-, and ERK 1/2-dependent NF-κB signalling versus the JNK/AP-1 pathway. Taken together, our findings suggest that disruption of the interaction between IL-17 and IL-23 may be a potential therapeutic approach in the treatment of periodontitis.

Zhu L ，Wu Y ，Wei H ，Xing X ，Zhan N ，Xiong H ，Peng B ... -  《-》