Different roles of PKC and PKA in effect of interferon-γ on proliferation and collagen synthesis of fibroblasts

• 来源期刊: 中国药理学报（英文版）
• 关键词: signal transduction protein kinase C protein kinase A interferon type II hypertrophic scar flbroblasts collagen synthesis
• 年，卷（期）: 2004,（10）
• 页码范围: 1320-1326
• 页数: 7页
• 语种: 英文

摘要

AIM: To study the signal roles of protein kinase C (PKC) and protein kinase A (PKA) in the influence of interferony (IFN-γ) on proliferation and collagen synthesis of fibroblasts derived from hypertrophic scar (HS-FB) and normal skin (NS-FB). METHODS: HS-FB and NS-FB were cultured and passaged in Dulbecco's modified Eagle's medium (DMEM). Activity of PKC and PKA were assayed by transferring phosphorus (32p) into substrate after treatment with IFN-γ 1000 kU/L at 10, 30, 60, and 120 min. Cell proliferation was determined with MTT assay.The collagen synthesis was measured with [3H]proline incorporation and Type III pre-collagen was determined with radioimmunoassay. RESULTS: After exposure to IFN-γ 1000 kU/L for 30 min, PKC activity of HS-FB and respectively (P＜0.05). After exposure to IFN-y 1000 kU/L for 60 and 120 min, PKA activities of HS-FB increased The PKA activities of NS-FB also increased from 0.52+0.03 nmol.min-1.g-1of control to 0.68±0.03 and 0.89±0.05 nmol.min-1.g-1, respectively (P＜0.05). The proliferation and collagen synthesis were enhanced by PKC activator (containing phosphatidylserine, diacylglycerol and Ca2+) and PKA inhibitor [H7250 μmol/L, 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine], and inhibited by PKC inhibior (GF109 250 μmol/L) and PKA activator (cAMP 25 rmol/L)(P＜0.01). GF109 abrogated increased proliferation and collagen synthesis by IFN-y but it did not affect the inhibitory effects of IFN-γ. At 120 min H7 reversed the inhibitory functions of IFN-γ. CONCLUSION: IFN-γ transiently increased proliferation and collagen synthesis of HS-FB and NS-FB by activation of PKC and subsequently inhibited proliferation and collagen synthesis by activation of PKA.