Premium
CD38‐cyclic ADP‐ribose‐mediated Ca 2+ signaling contributes to airway smooth muscle hyperresponsiveness
Author(s) -
Deshpande Deepak A.,
Walseth Timothy F.,
Panettieri Reynold A.,
Kannan Mathur S.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0450fje
Subject(s) - cyclic adp ribose , cd38 , ryanodine receptor , chemistry , medicine , endocrinology , nad+ kinase , cytokine , receptor , microbiology and biotechnology , biochemistry , biology , enzyme , stem cell , cd34
We previously demonstrated that cyclic ADP‐ribose (cADPR) elicits Ca 2+ release in airway smooth muscle (ASM) cells through ryanodine receptor channels. CD38 is a cell surface protein that catalyzes the synthesis and degradation of cADPR. In inflammatory diseases such as asthma, augmented Ca 2+ responses and Ca 2+ sensitivity contribute to increased ASM contractility in response to agonists. In this study, we investigated the regulation of CD38 expression and the role of cADPR‐mediated Ca 2+ release in airway inflammation. Human ASM cells in culture between the second and fifth passages were exposed to tumor necrosis factor α (TNF‐α), interleukin 1β, or interferon γ, or bovine serum albumin (controls). CD38 expression was measured by reverse transcriptase‐polymerase chain reaction (RT‐PCR), real‐time PCR, and Western blot analysis, and ADP‐ribosyl cyclase activity was assayed with nicotinamide guanine dinucleotide as the substrate. Ca 2+ responses to acetylcholine, bradykinin, and thrombin were measured in fura‐2AM‐loaded cells by fluorescence microscopy. Cytokines caused significant augmentation of CD38 expression, ADP‐ribosyl cyclase activity, and Ca 2+ responses to the agonists, compared with the control. TNF‐α effects were greater than those of the other two cytokines. The cADPR antagonist 8‐bromo‐cADPR attenuated the Ca 2+ responses to the agonists in control and cytokine‐treated cells, with the magnitude of inhibition correlating with the level of CD38. This study provides the first demonstration of a role for CD38‐cADPR signaling in a model of inflammatory airway disease.