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.
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.
R
R
Whelan
C
C
Kim
M
M
Chen
J
J
Leiter
M M
MM
Grunstein
H
H
Hakonarson
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