Modulation of calcium signaling by interleukin-13 in human airway smooth muscle: role of CD38/cyclic adenosine diphosphate ribose pathway.

Abstract

CD38/cyclic adenosine diphosphate ribose (cADPR) signaling plays an important role in the regulation of intracellular calcium responses to agonists in a variety of cells, including airway smooth muscle (ASM) cells. The present study was aimed at determining the effect of interleukin (IL)-13, a cytokine implicated in the pathogenesis of asthma, on CD38/cADPR signaling and to ascertain the contribution of CD38/cADPR signaling to IL-13-induced airway hyperresponsiveness. Human ASM cells maintained in culture were exposed to 50 ng/ml IL-13 for 22 h and levels of CD38 expression and intracellular calcium responses to agonists were measured. Treatment of human ASM cells with IL-13 resulted in increased CD38 expression as determined by real-time polymerase chain reaction, Western blot analysis, and indirect immunofluorescence. Increased CD38 expression was reflected as increased ADP-ribosyl cyclase activity in the ASM cell membranes. The net intracellular calcium responses to bradykinin, thrombin, and histamine were significantly (P < or = 0.05) higher in cells treated with IL-13 compared with controls. Furthermore, 8-bromo-cADPR, a cADPR antagonist, attenuated IL-13-induced augmented intracellular calcium responses to agonists in human ASM cells. These findings indicate that the CD38/cADPR-dependent pathway has a major role in IL-13-induced modulation of calcium signaling in human ASM.

• Authors: Deepak A Deshpande, Soner Dogan, Timothy F Walseth, Steven M Miller, Yassine Amrani, Reynold A Panettieri, Mathur S Kannan
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 31 Issue 1 Pg. 36-42 (Jul 2004) ISSN: 1044-1549 [Print] United States
• PMID: 14764428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD
• Bronchoconstrictor Agents
• Interleukin-13
• Membrane Glycoproteins
• Cyclic ADP-Ribose
• ADP-ribosyl Cyclase
• CD38 protein, human
• ADP-ribosyl Cyclase 1
• Calcium

Topics

• ADP-ribosyl Cyclase (immunology, physiology)
• ADP-ribosyl Cyclase 1
• Antigens, CD (immunology, physiology)
• Asthma (immunology, metabolism, physiopathology)
• Bronchi (immunology, metabolism, physiopathology)
• Bronchial Hyperreactivity (immunology, metabolism, physiopathology)
• Bronchoconstriction (drug effects, physiology)
• Bronchoconstrictor Agents (pharmacology)
• Calcium (metabolism)
• Calcium Signaling (drug effects, immunology)
• Cell Membrane (drug effects, immunology, metabolism)
• Cells, Cultured
• Cyclic ADP-Ribose (analogs & derivatives, antagonists & inhibitors, metabolism, pharmacology)
• Humans
• Interleukin-13 (immunology, metabolism, pharmacology)
• Intracellular Fluid (drug effects, metabolism)
• Membrane Glycoproteins
• Muscle, Smooth (immunology, metabolism, physiopathology)
• Myocytes, Smooth Muscle (drug effects, immunology, metabolism)
• Up-Regulation (drug effects, immunology)