We have shown that CGRP is up-regulated in invading macrophages in injured rat sciatic nerves and, through an autocrine or paracrine mechanism it contributes Angiogenesis inhibitor to the up-regulation of the pro-inflammatory cytokine interleukin-6 (IL-6) in invading macrophages.10 In rat peritoneal

macrophages, the endotoxin lipopolysaccharide (LPS) increased CGRP contents in a concentration-dependent manner.10 These data suggest that CGRP is produced by macrophages following inflammatory stimulation and its up-regulation in macrophages affects the functions of invading macrophages, hence influencing the outcome of inflammation. Monocytes/macrophages are the main effector cells of the immune system and play an essential role in host defence mechanisms against infectious micro-organisms and tumour cells. By secreting numerous biologically active molecules,

macrophages are involved not only in the regulation of the secondary immune response, but also in the process of inflammation and tissue repair. A growing body of evidence suggests that CGRP plays an important role in regulating the functions of macrophages, including the production of inflammation-related chemokines and cytokines. It is therefore important Rapamycin to understand how CGRP is up-regulated in macrophages during the inflammatory response and which functions of macrophages are modulated by CGRP. To address these issues, we used the RAW 264.7 murine macrophage cell line to obtain a large quantity of homogeneous macrophages and LPS as a prototype of inflammatory stimulus to examine the possible factors that can induce CGRP in RAW macrophages. The first aim of the present study was to determine whether LPS could induce CGRP in the RAW macrophage cell line. Lipopolysaccharide see more has been reported to up-regulate

the expression of inflammatory mediators such as IL-1β, tumour necrosis factor-α (TNFα), IL-6, nerve growth factor (NGF), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2) in RAW264.7 macrophages.11–13 The nuclear factor-κB (NF-κB) signalling pathway is involved in LPS-induced production of inflammatory mediators in this cell line.12,14 As a transcription factor, NF-κB plays a key role in the transcriptional regulation of genes of numerous inflammatory mediators including iNOS, COX2, IL-1β, IL-6 and TNFα.15 Among the inflammatory mediators, NGF,7,9 IL-1β,16,17 IL-618 and TNFα19 have been shown to induce CGRP in human B lymphocytes, monocytes, sensory neurons and various other cell types. Hence, the second aim of this study was to investigate the inflammatory mediators likely to be involved in LPS-induced CGRP in RAW macrophages and whether LPS-induced CGRP is mediated through the NF-κB signalling pathway.