Effect of Alarmins on the Synthesis of Tissue Cytokines

Abstract

A primary response of the innate immune system to a pathogen invasion or tissue damage is the synthesis of tissue cytokines. Interleukins (IL) 25 and 33 or thymic stromal lymphopoietin (TSLP) are produced by epithelial or muscle cells in response to pathogen fragments, i.e., pathogen associated molecular patterns (PAMPs) or endogenous stress factors (danger associated molecular patterns, DAMPs). The goal of this work is to compare the ability of the bacterial peptide N-formyl-met-leu-phe (fMLP) and an endogenous pruritus inducer, amino acid β-alanine, to stimulate the expression of tissue cytokines. It has been shown by quantitative PCR that fMLP stimulates the ex vivo gene expression of TSLP and IL-25 in murine trachea explants, and β-alanine also stimulates IL-33 gene expression. The in vivo level of TSLP and IL-33 has been evaluated by ELISA in lung homogenates 1 and 6 h after intratracheal injection of the stimulants. Both β‑alanine and fMLP induce the release of IL-33 and TSLP from the intracellular depot. It is shown for the first time that β-alanine and fMLP are activators of tissue cytokine synthesis.