Substance P regulates somatostatin expression in inflammation

Area of Science:

• Immunology
• Neuroendocrinology
• Parasitology

Background:

• Substance P (SP) and somatostatin (SOM) are key immunomodulators at mucosal surfaces and inflammation sites.
• A SP/SOM circuit influences IFN-gamma response in murine schistosomiasis, with SP enhancing and SOM decreasing IFN-gamma.
• While inflammatory mediators induce SOM in macrophages, a factor limiting its expression was unknown.

Purpose of the Study:

• To investigate the regulatory role of SP on SOM synthesis in macrophages.
• To determine if SP affects SOM expression in both normal and schistosome-infected mouse models.
• To elucidate the mechanism of SP-mediated regulation of SOM.

Main Methods:

• Quantitative PCR to measure SOM mRNA levels in splenocytes and granuloma cells.
• Measurement of SOM protein content in splenocytes.
• Immunohistochemistry to localize SOM expression in splenic macrophages.
• Administration of SP and SP receptor antagonists to assess effects on SOM expression.
• In vitro culture of splenocytes and granuloma cells with various stimuli.

Main Results:

• SP significantly inhibited SOM mRNA and protein expression in splenocytes from normal mice stimulated with LPS, IFN-gamma, or IL-10.
• SP markedly reduced constitutive SOM mRNA expression in macrophages within granulomas of Schistosoma mansoni-infected mice.
• SP receptor antagonists blocked the inhibitory effect of SP, confirming receptor-mediated action.
• IL-4 was found to antagonize the SP-induced suppression of SOM in splenocytes.

Conclusions:

• SP inhibits both the induction and ongoing expression of SOM in macrophages at the mRNA and protein levels via the SP receptor.
• This SP-mediated regulation of SOM occurs in both non-infected and Schistosoma mansoni-infected mice.
• IL-4 can counteract the inhibitory effects of SP on SOM expression, suggesting a complex regulatory network.