IL-4 and IL-13 stimulate human bronchial epithelial cells to release IL-8.
Cytokine networks are important in regulating the traffic of inflammatory cells in the airways. Interleukin-8 (IL-8) released by human bronchial epithelial cells (HBECs) is thought to be of particular importance in attracting neutrophils and monocytes to sites of inflammation. Increased release of IL-8 by HBECs in response to Th-1 cytokines such as TNF alpha and IL-1 beta may be an important pathophysiologic pathway. The present study was designed to explore the role of the Th2 cytokine IL-4 and the functionally related interleukins IL-10, and IL-13 on the regulation of IL-8 release by HBECs. HBECs (passage 4-6) were cultured in LHC9/RPMI and when confluent cells were stimulated in unsupplemented medium LHCD/RPMI by IL-4, IL-10, and IL-13 at 10 ng/ml concentration for all cytokines. TNF alpha stimulation was used as a positive control. After 24 hours supernatants were collected and tested for IL-8 by a sandwich ELISA. Unstimulated HBECs spontaneously released limited amounts of IL-8 (11 +/-1 pM) and significantly increased cytokine production in response to IL-4 (42 +/- 1 pM), IL-13 (30 +/- 1 pM) and TNF (128 +/- 11 pM). Stimulation with IL-10 (11 +/- pM) did not change basal production of IL-8. When HBECs were co-stimulated with IL-4 plus TNF, the production of IL-8 was further increased (204 +/- 5 pM). In contrast, IL-10 attenuated the effect of TNF during co-stimulation (82 +/- 5 pM). IL-13 did not affect the release of IL-8 induced by TNF (111 +/- 9 pM). Northern blot analysis of IL-8 mRNA levels showed the highest induction of IL-8 mRNA in HBECs co-stimulated with TNF and IL-4. We conclude from our study that IL-4 directly induces IL-8 release from HBECs and amplifies the release of IL-8 in response to TNF alpha. IL-13 is less active and IL-10 has an inhibitory effect. Airway epithelial cells are able to interact, therefore, with products of both Th1 and Th2 cells with respect to modulating release of IL-8.
Stríz
I
I
Department of Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Mio
T
T
Adachi
Y
Y
Robbins
R A
RA
Romberger
D J
DJ
Rennard
S I
SI
D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism*
D018793:Interleukin-13; D016209:Interleukin-8; D015847:Interleukin-4