Effect of Interleukin-1β and Tumor Necrosis Factor-α on the Expression of G-Proteins in CD4⁺ T-Cells of Atopic Asthmatic Subjects

Abstract

Chronic use of β₂-agonists and increased production of inflammatory mediators during the late allergic reaction after the antigen challenge result in the desensitization of β-adrenoceptors in the airways with an accompanying rise in nonspecific airway hyperresponsiveness. Several proinflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), play a significant role in orchestrating and perpetuating the inflammatory response and induce the decreased response to bronchodilators in vitro. However, the underlying mechanisms are unknown. In this study, we examined the effect of two cytokines, IL-1β and TNF-α, on the expression of guanine nucleotide binding regulatory proteins (G-proteins), G_sα and G_iα-3, by Western blotting in the CD4⁺ cells of nonatopic nonasthmatic (NANA), atopic nonasthmatic (ANA), and atopic asthmatic (AA) subjects. In the purified CD4⁺ cells, the basal expression of G_sα was higher in the ANA group, and significantly lower in the AA group as compared to the NANA group. The basal expression of G_iα-3 was significantly greater (3–15 fold) than G_sα, with no significant difference between any of the three groups. Both cytokines IL-1β and TNF-α significantly decreased the expression of G_sα in the CD4⁺ cells of the NANA and ANA groups, with no effect in the AA group. However, these cytokines increased the expression of G_iα-3, proteins in the AA group, but had no effect in the CD4⁺ cells of the NANA and ANA groups. These data suggest that a decreased response to β₂-agonists in the late allergic response in allergic asthmatic subjects could be due to the release of inflammatory cytokines, which induce a decrease in the stimulatory G-proteins and an increase in the inhibitory G-proteins.

• Airway hyperresponsiveness
• Asthma
• Cytokines
• G-proteins
• IL-1β
• Inflammation
• TNF-α