Growth hormone releasing peptide ia a natual product ,and has anti-inflammatory effects, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A.

Growth hormone releasing peptide-2 (GHRP-2)?attenuated phorbol 12, 13-didecanoate (PDD)-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE?) 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[1].

KGN cells were pretreated with Growth hormone releasing peptide-2(GHRP-2 )(1 μM) or with GHRP-2 in combination with an inhibitor, either a MKP-1 inhibitor (sanguinarine;?0.01, 0.1, and 1 μM) or a PP2A inhibitor (okadaic acid;?10, and 30 μM) for 2 h before the addition of PDD for an additional 12 h. Sanguinarine at 0.1 or 1 μM was able to attenuate the suppression effect of GHRP-2 on PDD-induced COX-2 expression and at 1 μM, it was also able to attenuate the inhibitory effect of GHRP-2 on PDD-induced IL-8 expression[1].