Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica ›› 2006, Vol. 28 ›› Issue (6): 781-785.

• Original Articles • Previous Articles     Next Articles

Signaling Pathways in Expression of Inducible Nitric Oxide Synthase Induced byHigh Mobility Group Box 1 in Rat Alveolar Macrophages

YU Yue, REN Da-bin, SUN Ren-yu, WANG Shi-wen   

  1. Department of Pathophysiology, Institute of Basic Medical Sciences, CAMS and PUMC, Beijing 100005,China
  • Received:2006-03-30 Revised:1900-01-01 Online:2006-12-30 Published:2006-12-30
  • Contact: SUN Ren-yu

Abstract: ABSTRACT:Objective To explore roles of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen activated protein kinase(p38 MAPK) and nuclear factor (NF)-κB in expression of inducible nitric oxide synthase (iNOS) in rat alveolar macrophages induced by high mobility group box 1 (HMGB1). Methods Primary rat alveolar macrophages (PRAMs) cultured in vitro were incubated with PD98059 (inhibitor against ERK), SB203580 (inhibitor against p38 MAPK), PDTC (inhibitor against NF-κB),or PD98059 plus SB203580 for 2 hours,respectively. HMGB1 was added into the cultures and incubated with cells for 6 hours. Total RNA of PRAMs was extracted and iNOS mRNA expression was semi-quantified with reverse transcription-polymerase chain reaction (RT-PCR). Greiss reaction was applied to determine nitrite/nitrate (NO-2/NO-3) concentration in PRAMs culture supernatants. Results Expression of iNOS mRNA and NO production in PRAMs culture supernatants were down-regulated by inhibition of ERK or p38 MAPK by PD98059 or SB203580, respectively (P<0.05=. Moreover, inhibition of iNOS expression and NO production was observed after simultaneous pretreatment with PD98059 and SB203580(P<0.05=. Expression of iNOS mRNA in PRAMs and NO production in PRAMs culture supernatants were down-regulated by inhibition ofNF-κB by PDTC(P<0.05). Conclusion Cellular signal molecules of ERK, p38 MAPK,and NF-κB all participate in the expression of iNOS and NO production in PRAMs induced by HMGB1.

Key words: dicd mobility croup box 1, alveolar macropdace, inducible nitric oxide syntdase