Role and regulation of interleukin-1 molecules in pro-asthmatic sensitised airway smooth muscle.
Interleukin (IL)-1beta is a pleiotropic, pro-inflammatory cytokine that has been importantly implicated in driving the inflammatory response and resultant changes in airway smooth muscle (ASM) responsiveness in asthma. IL-1beta belongs to a family of molecules, known as the IL-1 axis, which exert both pro- and anti-inflammatory effects. Since dysregulation of IL-1 axis molecules may be critical in the pathobiology of asthma, the present study examined the expression and activation of both the inhibitory and stimulatory IL-1 axis molecules in human ASM cells and their roles in modulating cytokine and immunoglobulin (Ig)E immune complex (IgE cx)-mediated changes in rabbit ASM constrictor and relaxant responsiveness. The results demonstrate the following. 1) Pre-treatment of isolated rabbit tracheal rings with the inhibitory IL-1 axis members, IL-1 receptor antagonist and IL-1 type-II receptor abrogated both IL-5- and IgE cx-induced changes in ASM responsiveness. 2) Administration of IL-5, IL-1beta and IgE cxs to human ASM cells increased mRNA and protein expressions of both stimulatory and inhibitory IL-1 axis molecules. 3) The time course of IL-5-induced IL-1 axis molecule expression preceded that of both IL-1beta and IgE immune cxs. Collectively, these findings suggest that modulation at the level of the interleukin-1 axis of molecules may have significant therapeutic potential in the treatment of asthma.
Whelan
R
R
Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA.
Kim
C
C
Chen
M
M
Leiter
J
J
Grunstein
M M
MM
Hakonarson
H
H
D000818:Animals; D001249:Asthma / Q000276:immunology; D001980:Bronchi / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology / Q000502:physiology; D009130:Muscle, Smooth / Q000276:immunology*; D011817:Rabbits
D016207:Cytokines; D007375:Interleukin-1; D015848:Interleukin-5; D007073:Immunoglobulin E