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We hypothesized that participation of sensory neuropeptides, substance P and neurokinin A in the airway in- flammation caused to resistance against the glucocorticoids (GCs) treatment. We have measured the expression level of cytokines and chemokines mRNAs in bronchoalveolar lavage cells (BAL), transbronchial lung biopsies (TBLB) and peripheral blood mononuclear cells (PBMC) by reverse transcriptase polymerase chain reaction (RT- PCR). The mRNAs of interleukin-4 (IL-4) and -5, which are typical Thelper 2 (Th2)-type cytokines, were scarcely detected in all of bronchoalvelar lavage fluid (BALF) and TBLB samples. But the mRNA of Th1-type cytokines, such as IL-12, IL-18, and interferon-γ (IFN-γ), tended to be expressed higher than that of Th2-type cytokines at the early stage of asthma before intervention with GCs. The mRNAs of IL-18, IFN-γ, macrophage-derived chemokine (MDC) and thymus- and activation-regulated chemokine (TARC) tended to be expressed higher than that of non- asthmatic subjects. In vitro study demonstrated that the expression of TARC mRNA induced by the combination of IL-4, IFN-γ, and neurokinin A in human bronchial epithelial cells, BEAS-2B was not inhibited by the treatment of the cells with dexamethasone even at 10-6 M. We proposed that the part of resistance to GCs in the asthmatic patient without GC receptor β expression might be associated with the induction of TARC expression in airway epithelial cells by tachykinines and histamine.

journal of health science

Effects of Tachykinins and Histamine on the Expression of Thymus- and Activation-Regulated Chemokine mRNA in Peripheral Blood Mononuclear Cells and Human Bronchial Epithelial Cells.