TY - JOUR
T1 - Thymic stromal lymphopoietin in cigarette smoke-exposed human airway smooth muscle
AU - Smelter, Dan F.
AU - Sathish, Venkatachalem
AU - Thompson, Michael A.
AU - Pabelick, Christina M.
AU - Vassallo, Robert
AU - Prakash, Y. S.
PY - 2010/9/1
Y1 - 2010/9/1
N2 - Thymic stromal lymphopoietin (TSLP) is a newly identified IL-7-like cytokine known to be expressed in airway biopsies of patients with asthmaand chronic obstructive pulmonary disease. As both diseases may be induced or exacerbated by cigarette smoking, it is possible that TSLP represents an important link between cigarette smoke exposure and inflammatory signaling in the airways. In this regard, TSLP appears to also be expressed in airway smooth muscle (ASM); however, its role is unknown. In the current study, we examined TSLP and the TSLP receptor (TSLP-R) expression and function in human ASM cells under normal conditions and following exposure to cigarette smoke extract (CSE). Western blot analysis of human ASM cells showed significant expression of TSLP and TSLP-R, with increased expression of both by overnight exposure to 1 or 2% CSE. Furthermore, CSE increased TSLP release by ASM. In parallel experiments using enzymatically dissociated human ASM cells loaded with the Ca2+ indicator fura 2-AM and imaged using fluorescence microscopy, we evaluated the effects of CSE exposure on intracellular Ca2+ ([Ca2+] i) responses to agonist stimulation. [Ca2+]i responses to histamine were increased with overnight CSE exposure. Exposure to TSLP also resulted in elevated responses, which were blunted by TSLP and TSLP-R Abs. Importantly, the enhancing effects of CSE on [Ca2+]i responses were also blunted by these Abs. These effects were associated with CSE- and TSLP-induced changes in STAT5 phosphorylation. Overall, these novel data suggest that cigarette smoke, TSLP, and ASM are functionally linked and that cigarette smoke-induced increase in airway contractility may be mediated via ASM-derived increases in TSLP signaling.
AB - Thymic stromal lymphopoietin (TSLP) is a newly identified IL-7-like cytokine known to be expressed in airway biopsies of patients with asthmaand chronic obstructive pulmonary disease. As both diseases may be induced or exacerbated by cigarette smoking, it is possible that TSLP represents an important link between cigarette smoke exposure and inflammatory signaling in the airways. In this regard, TSLP appears to also be expressed in airway smooth muscle (ASM); however, its role is unknown. In the current study, we examined TSLP and the TSLP receptor (TSLP-R) expression and function in human ASM cells under normal conditions and following exposure to cigarette smoke extract (CSE). Western blot analysis of human ASM cells showed significant expression of TSLP and TSLP-R, with increased expression of both by overnight exposure to 1 or 2% CSE. Furthermore, CSE increased TSLP release by ASM. In parallel experiments using enzymatically dissociated human ASM cells loaded with the Ca2+ indicator fura 2-AM and imaged using fluorescence microscopy, we evaluated the effects of CSE exposure on intracellular Ca2+ ([Ca2+] i) responses to agonist stimulation. [Ca2+]i responses to histamine were increased with overnight CSE exposure. Exposure to TSLP also resulted in elevated responses, which were blunted by TSLP and TSLP-R Abs. Importantly, the enhancing effects of CSE on [Ca2+]i responses were also blunted by these Abs. These effects were associated with CSE- and TSLP-induced changes in STAT5 phosphorylation. Overall, these novel data suggest that cigarette smoke, TSLP, and ASM are functionally linked and that cigarette smoke-induced increase in airway contractility may be mediated via ASM-derived increases in TSLP signaling.
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U2 - 10.4049/jimmunol.1000252
DO - 10.4049/jimmunol.1000252
M3 - Article
C2 - 20660708
AN - SCOPUS:78049388373
SN - 0022-1767
VL - 185
SP - 3035
EP - 3040
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -