Expression and Release of Interleukin-8 by Human Airway Smooth Muscle Cells: Inhibition by Th-2 Cytokines and Corticosteroids

Abstract

Interleukin (IL)-8 is a C-X-C chemokine that potently chemoattracts and activates neutrophils. We determined whether IL-8 could be produced by human airway smooth muscle cells in culture and examined its regulation. TNF-alpha stimulated IL-8 mRNA expression and protein release in a time- and dose-dependent manner, whereas IFN-gamma alone had no effect. Both cytokines together did not induce greater IL-8 release compared to TNF-alpha alone. IL-1beta was more potent in inducing IL-8 release and, together with TNF-alpha, there was a synergistic augmentation of IL-8 release. IL-8 release induced by TNF-alpha and IFN-gamma was partly inhibited by the Th-2-derived cytokines IL-4, IL-10, and IL-13, as well as by dexamethasone. In addition to its contractile responses, airway smooth muscle cells have synthetic and secretory potential with the release of IL-8 and subsequent recruitment and activation of neutrophils in the airways. Release of IL-8 can be modulated by Th-2-derived cytokines and corticosteroids.

Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

“…IL-8, RAN-TES, and eotaxin production by human ASMC is induced by TNF-␣ but not IFN-␥. Furthermore, although IFN-␥ potentiates TNF-␣-induced RANTES release, it has no synergistic effects on TNF-␣-induced IL-8 or eotaxin release (11,35,36,51). Thus the relative presence or absence of IFN-␥ and TNF-␣ in the inflammatory milieu may direct the pattern of ASMC chemokine synthesis and hence the type of inflammatory cells recruited.…”

“…Corticosteroids are the most effective anti-inflammatory drugs for the treatment of asthma, and previous studies have demonstrated inhibitory effects of corticosteroids on ASMC cytokine and chemokine synthesis (35,36). Paradoxically, we observed marked upregulation of cytokine-stimulated FKN mRNA expression and protein synthesis in the presence of the corticosteroid dexamethasone.…”

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

“…There is no evidence for the release of macrophage inflammatory protein-1a [30]. Following stimulation with IL-1b and bradykinin, airway smooth muscle cells can express and release IL-8, a potent neutrophil chemoattractant [35,36].…”

Corticosteroid Inhibition of Growth-Related Oncogene Protein-α via Mitogen-Activated Kinase Phosphatase-1 in Airway Smooth Muscle Cells

“…H uman airway smooth muscle cells (ASMC), 3 apart from having contractile and proliferative functions, may contribute directly to airway inflammation through their synthesis of proinflammatory cytokines and chemokines (1). ASMC in culture can be stimulated to produce a wide array of cytokines and chemokines, such as GM-CSF, RANTES, eotaxin, IL-6, IL-8, and growth-related oncogene protein-␣ (GRO-␣) in response to inflammatory mediators (2-7), and may therefore be important effector cells in lung inflammation.…”