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Differential expression of inducible nitric oxide synthase and IL-12 between peritoneal and splenic macrophages stimulated with LPS plus IFN-γ is associated with the activation of extracellular signal-related kinase
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- المؤلفون: Zhu, Yi-Na; Yang, Yi-Fu; Ono, Shiro; Zhong, Xiang-Gen; Feng, Yong-Hong; Ren, Yong-Xin; Ni, Jia; Fu, Yun-Feng; Tang, Wei; Zuo, Jian-Ping
- المصدر:
International Immunology; June 2006, Vol. 18 Issue: 6 p981-990, 10p
- معلومة اضافية
- نبذة مختصرة :
Resident peritoneal macrophages (pMϕ) are found deficient in T cell-stimulating capacity compared with the competent splenic macrophages (sMϕ). Macrophages (Mϕ)-derived nitric oxide (NO) and IL-12 have been shown to play crucial roles in the interaction between Mϕ and T cells. To further understand differential functions between pMϕ and sMϕ, we focused on the production of NO and IL-12 from LPS plus IFN-γ-activated Mϕ. We demonstrated the differential expression of inducible nitric oxide synthase (iNOS) and IL-12 in pMϕ and sMϕ with LPS plus IFN-γ stimulation. pMϕ produced high level of NO but low level of IL-12, whereas sMϕ produced high level of IL-12 but no NO. Furthermore, we demonstrated that there were no differences in IFN-γ-induced signal transducer and activator of transcription-1 activation and consequent interferon regulatory factor-1 and interferon consensus sequence-binding protein up-regulation between pMϕ and sMϕ. Likewise, p38 mitogen-activated protein kinase was activated by LPS with identical kinetics in both pMϕ and sMϕ. However, LPS-induced extracellular signal-regulated kinase (ERK) activation was prolonged in pMϕ comparing with sMϕ. Moreover, we demonstrated, using inhibitor selective for ERK cascade (PD98059), that the prolonged ERK activation contributed a positive signal for iNOS expression and a negative signal for IL-12p40 expression in resident pMϕ. In addition, anti-IL-10-neutralizing antibody plus indomethacin could abrogate the inhibitory effects of endogenous IL-10 and prostaglandin E2 on the production of IL-12 by resident pMϕ possibly through suppressing ERK activation. Taken together, profound difference in ERK activation may account for differential LPS plus IFN-γ responsiveness between pMϕ and sMϕ. High production of NO and low production of IL-12 by pMϕ may contribute to its deficiency in T cell-stimulating capacity.
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