TY - JOUR
T1 - Effect of interleukin-1β and tumor necrosis factor-α on the expression of G-proteins in CD4+ T-cells of atopic asthmatic subjects
AU - Kim, Matthew H.
AU - Agrawal, Devendra K.
PY - 2002
Y1 - 2002
N2 - 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 non-specific 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), Gsα and Giα-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 Gsα was higher in the ANA group, and significantly lower in the AA group as compared to the NANA group. The basal expression of Giα-3 was significantly greater (3-15 fold) than Gsα, with no significant difference between any of the three groups. Both cytokines IL-1β and TNF-α significantly decreased the expression of Gsα in the CD4+ cells of the NANA and ANA groups, with no effect in the AA group. However, these cytokines increased the expression of Giα-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 β2agonists in the late allergic response in allergis 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.
AB - 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 non-specific 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), Gsα and Giα-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 Gsα was higher in the ANA group, and significantly lower in the AA group as compared to the NANA group. The basal expression of Giα-3 was significantly greater (3-15 fold) than Gsα, with no significant difference between any of the three groups. Both cytokines IL-1β and TNF-α significantly decreased the expression of Gsα in the CD4+ cells of the NANA and ANA groups, with no effect in the AA group. However, these cytokines increased the expression of Giα-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 β2agonists in the late allergic response in allergis 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.
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U2 - 10.1081/JAS-120004037
DO - 10.1081/JAS-120004037
M3 - Article
C2 - 12214898
AN - SCOPUS:0036024619
VL - 39
SP - 441
EP - 448
JO - Journal of Asthma
JF - Journal of Asthma
SN - 0277-0903
IS - 5
ER -