Tnf[alpha] and il-1[beta] upregulate nitric oxide-dependent ciliary motility in bovine airway epithelium. Jain, Bharat, Israel Rubinstein*, Richard A. Robbins, and Joseph H. Sisson. Pulmonary and Critical Care Medicine Section, Departments of Medicine and Physiology and Biophysics, University of Nebraska Medical Center and Research Service, Omaha Veterans Affairs Medical Center, Omaha, NE
APStracts 2:0003L, 1995.
Airway epithelial cells can be modulated by cytokines such as TNF[alpha] and IL-1[beta] that are released from inflammatory cells. Since ciliary motility is an important host defense function of airway epithelium, we hypothesized that cytokines, released from lung macrophages, upregulate ciliary motility. To test this hypothesis, ciliary beat frequency (CBF) was measured by video microscopy in cultured ciliated bovine bronchial epithelial cells (BBECs) incubated for 24 hrs with bovine alveolar macrophage-conditioned media (AM -CM). Exposure to AM-CM resulted in a delayed (>/= 2 hours) increase in CBF that was maximal following 24 hrs exposure (13.70 +/- 0.43 Hz for AM-CM vs 9.44 +/- 0.24 Hz for media; p < 0.0001) and which was largely blocked by either anti -TNF[alpha] or anti-IL-1[beta] antibodies. rTNF[alpha] or rIL- 1[beta] similarly increased CBF which could be blocked by preincubation with either anti-rTNF[alpha] or anti-rIL-1[beta] antibodies. Pre-incubation of BBECs with actinomycin-D or dexamethasone also blocked rTNF[alpha]- and rIL- 1[beta]-induced cilia stimulation suggesting that new protein synthesis is required for cytokine-induced upregulation of CBF. Since nitric oxide (NO) is known to upregulate ciliary motility and cytokines can induce NO synthase (NOS), we hypothesized that TNF[alpha] and IL-1[beta] increase CBF by inducing NOS in BBECs. The cilia stimulatory effects of TNF[alpha] or IL- 1[beta] were inhibited by NG-monomethyl L-arginine, a competitive NOS inhibitor, and restored by the addition of either L-arginine, a NOS substrate, or sodium nitroprusside, a NO donor. These studies show that TNF[alpha] or IL- 1[beta] can upregulate ciliary motility presumably by releasing NO via induction of iNOS and suggests a mechanism by which inflammation increases ciliary motility. 

Received 10 June 1994; accepted in final form 6 January 1995.
APS Manuscript Number L0171-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.