RRC ID 51831
Author Chao YN, Sun D, Peng YC, Wu YL.
Title Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells.
Journal Int J Mol Sci
Abstract Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two important inflammatory mediators in ovulation. Ghrelin may modulate inflammatory signaling via growth hormone secretagogue receptors. We investigated the role of ghrelin in KGN human ovarian granulosa cells using protein kinase C (PKC) activator phorbol 12, 13-didecanoate (PDD) and synthetic ghrelin analog growth hormone releasing peptide-2 (GHRP-2). GHRP-2 attenuated PDD-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE₂) and IL-8. GHRP-2 promoted the degradation of PDD-induced COX-2 and IL-8 proteins with the involvement of proteasomal and lysosomal pathways. PDD-mediated COX-2 production acts via the p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways; PDD-mediated IL-8 production acts via the p38, JNK and ERK pathways. GHRP-2 reduced the PDD-induced phosphorylation of p38 and JNK and activator protein 1 (AP-1) reporter activation and PDD-induced NF-κB nuclear translocation and reporter activation. The inhibitors of mitogen-activated protein kinase phosphatase-1 (MKP-1) and protein phosphatase 2 (PP2A) reduced the inhibitory effect of GHRP-2 on PDD-induced COX-2 and IL-8 expression. Our findings demonstrate an anti-inflammatory role for ghrelin (GHRP-2) in PKC-mediated inflammation of granulosa cells, at least in part, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A.
Volume 17(8)
Published 2016-8-19
DOI 10.3390/ijms17081359
PII ijms17081359
PMID 27548147
PMC PMC5000754
MeSH Cell Line, Tumor Cyclooxygenase 2 / metabolism Enzyme-Linked Immunosorbent Assay Female Ghrelin / metabolism Granulosa Cells / drug effects Granulosa Cells / metabolism* Humans Inflammation / drug therapy* Inflammation / etiology Inflammation / metabolism Interleukin-8 / metabolism Oligopeptides / pharmacology* Phorbol Esters / pharmacology Protein Kinase C / metabolism* Reverse Transcriptase Polymerase Chain Reaction Transcription Factor AP-1 / metabolism
IF 4.183
Human and Animal Cells KGN(RCB1154)