Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells.
Chao. Yi-Ning YN; Sun. David D; Peng. Yen-Chun YC; Wu. Yuh-Lin YL
Key Findings
- GHRP‑2 reduced the protein and mRNA levels of COX‑2 and IL‑8, two key inflammatory mediators, in ovarian granulosa cells.
- The peptide promoted degradation of these proteins via both proteasome and lysosome systems.
- GHRP‑2 blocked activation of the p38, JNK, ERK, and NF‑κB pathways that normally increase COX‑2 and IL‑8 production.
Practical Outcomes
- The study suggests that GHRP‑2 may have anti‑inflammatory effects beyond its known role in stimulating growth hormone. However, the work was done only in isolated ovarian cells, so it does not yet tell us how the peptide will affect whole‑body inflammation, dosage, or safety for everyday use. Biohackers should view this as early mechanistic evidence, not a direct protocol change.
Summary
In lab tests on human ovarian cells, the synthetic ghrelin‑like peptide GHRP‑2 lowered inflammation markers that are usually turned on by a strong cell‑activating chemical. It did this by speeding up the breakdown of inflammatory proteins and by dampening several signaling pathways that drive inflammation.
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.
Study Information
pubmed
2016
2016-08-19T00:00:00.000Z
10.3390/ijms17081359
2
75