Biomedical subjects

J H Sisson

Publications and source records attributed to J H Sisson.

At least 19 recordsLinked to original sources

PubMed2005

Adenosine A2A receptors promote adenosine-stimulated wound healing in bronchial epithelial cells.

Adenosine produces a wide variety of physiological effects through the activation of specific adenosine receptors (A(1), A(2A), A(2B), A(3)). Adenosine, acting particularly at the A(2A) adenosine receptor (A(2A)AR), is a potent endogenous anti-inflammatory agent and sensor of inflammatory tissue damage. The complete healing of wounds is the final step in a highly regulated response to injury. Recent studies on epidermal wounds have identified the A(2A)AR as the main adenosine receptor responsible for altering the kinetics of wound closure. We hypothesized that A(2A)AR promotes wound healing in bronchial epithelial cells (BECs). To test this hypothesis, the human BEC line BEAS-2B and bovine BECs (BBECs) were used. Real-time RT-PCR of RNA from unstimulated BEAS-2B cells revealed transcriptional expression of A(1), A(2A), A(2B) and A(3) receptors. Western blot analysis of lysates from BEAS-2B cells and BBECs detected a single band at 44.7 kDa in both the BECs, indicating the presence of A(2A)AR. In a wound healing model, we found that adenosine stimulated wound repair in cultured BBECs in a concentration-dependent manner, with an optimal closure rate observed between 4 and 6 h. Similarly, the A(2A)AR agonist 5'-(N-cyclopropyl)carboxamidoadenosine (CPCA) augmented wound closure, with a maximal closure rate occurring between 4 and 6 h. Inhibition of A(2A)AR with ZM-241385, a known A(2A)AR antagonist, impeded wound healing. In addition, ZM-241385 also attenuated adenosine-mediated wound repair. Kinase studies revealed that adenosine-stimulated airway repair activates PKA by ligating A(2A)AR. Collectively, the data suggest that the A(2A)AR is involved in BEC adenosine-stimulated wound healing and may prove useful in understanding purinergic-mediated actions on airway epithelial repair.

Adenosine↗

PubMed2004

IL-8 inhibits isoproterenol-stimulated ciliary beat frequency in bovine bronchial epithelial cells.

Mucociliary clearance is a critical host defense that protects the lung. The mechanisms by which mucociliary function is altered by inflammation are poorly defined. Chronic exposure to cigarette smoke decreases ciliary beating and interferes with proper airway clearance. Bronchoalveolar lavage (BAL) fluid from smokers and ex-smokers has increased amounts of IL-8, which has played a critical role in airway inflammation. We hypothesized that IL-8 might interfere with stimulated ciliary beating in airway epithelium. To test this hypothesis, we stimulated bovine ciliated bronchial epithelial cells (BBECs) with a known activator of ciliary beat frequency (CBF), isoproterenol (ISO; 100 microM), in the presence or absence of IL-8 (100 pg/mL). We measured CBF digitally using the Sisson-Ammons Video Analysis (SAVA) system. CBF increased in untreated cells exposed to ISO (approximately 3 Hz) over baseline. In contrast, cells pre-incubated with IL-8 failed to respond to ISO. Pretreatment with IL-8 also blocked ISO-stimulated cAMP-dependent kinase (PKA) activation, which is known to control ISO-stimulated CBF. In addition, IL-8 pretreated cells revealed a marked decrease in PKA activity when cells were stimulated with forskolin (FSK; 10 microM). Cells were assayed specifically for cAMP-phosphodiesterase (PDE) activity. ISO-stimulated cells demonstrated an increase in PDE activity as compared to control. Pretreatment with IL-8 had no effect on ISO-stimulated PDE activity. Collectively, these data suggest that IL-8 appears to mediate its effect at the level of adenylyl cyclase. It is also possible that IL-8 may not only act as a chemotactic agent, but also as a potential autocrine/paracrine inhibitor of PKA-mediated stimulation of ciliary motility. In conclusion, IL-8 inhibits beta-agonist dependent ciliostimulation and such inhibition of stimulated ciliary activity may contribute to the impaired mucociliary clearance seen in airway diseases. Furthermore, since IL-8 levels are increased in the airway of cigarette smokers, it is likely they may be more resistant to the cilio and muco-ciliostimulating effects of beta-agonists.

Animals↗

PubMed2003

All-digital image capture and whole-field analysis of ciliary beat frequency.

We hypothesized that a high-speed all-digital video imaging system, with computerized analysis, would precisely capture and measure ciliary beat frequency (CBF) and would shorten the time from data capture to data analysis. We compared a conventional analog video system with a new high-speed digital system we developed for CBF analysis. Using ciliated primary bovine bronchial epithelial cells we made simultaneous analog and digital CBF measurements of the same region of interest (ROI) while temperature was varied. This yielded nearly identical data over a wide range of frequencies (7-15 Hz) using either system. Unlike the digital system however, the analog system did not accurately detect CBF above 15 Hz (temperatures higher than 30 degrees C). We also compared ROI analysis with a new analysis algorithm we have named whole-field analysis (WFA). WFA measurement of CBF agreed with ROI and reduced operator time required to analyse data by more than 90% compared with the analog system. We conclude that all-digital computerized CBF analysis correlates closely with standard video methods, markedly speeds up data analysis and provides new ways, including WFA, to analyse entire fields of motile cilia simultaneously. We have termed this system 'Sisson-Ammons Video Analysis' (SAVA).

Animals↗

PubMed2002

Relaxin stimulates bronchial epithelial cell PKA activation, migration, and ciliary beating.

Relaxin is an insulin-like serum protein secreted during pregnancy and found in many tissues, including the lung. Relaxin is reported to stimulate epithelial cell proliferation, but the effects of relaxin on airway epithelium are unknown. We tested the hypothesis that relaxin would stimulate the increased migration of bronchial epithelial cells (BEC) in response to wounding. Using monolayers of BEC in a wound-healing model, relaxin augmented wound closure with maximal closure occurring at 12 hr (1 micro M). Unlike cytokines, relaxin did not stimulate increased BEC interleukin-8 (IL-8) release. Relaxin caused a significant stimulation of ciliary beat frequency (CBF) in BEC. Because protein kinase (PKA) activation increases CBF and relaxin can elevate intracellular cAMP levels, we measured PKA activity in BEC treated with relaxin. Relaxin increased PKA activity 3-4 fold by approximately 4 hr, with a return to baseline levels by 8-10 hr. Relaxin-stimulated PKA activity differs temporally from the rapid (1 hr) beta-adrenergic activation of PKA in BEC. These data suggest that relaxin augments epithelial repair by increasing airway cell migration and CBF via PKA-dependent mechanisms.

Animals↗

PubMed2001

Malondialdehyde-acetaldehyde-adducted bovine serum albumin activates protein kinase C and stimulates interleukin-8 release in bovine bronchial epithelial cells.

Previous study results have demonstrated that cigarette smoke or acetaldehyde rapidly stimulates protein kinase C (PKC)-mediated release of interleukin-8 (IL-8) in bovine bronchial epithelial cells (BECs). Low concentrations of acetaldehyde combine synergistically with malondialdehyde to increase significantly maximal BEC PKC activity at 48 to 96 h stimulation. Because more than 95% of alcoholics are cigarette smokers, we hypothesized that malondialdehyde, an inflammation product of lipid peroxidation, and acetaldehyde, both a product of ethanol metabolism and a component of cigarette smoke, might stimulate PKC-mediated IL-8 release in BECs by malondialdehyde-acetaldehyde (MAA) adduct formation, rather than as free aldehydes. Protein kinase C activity is maximally elevated in BECs treated with 50 microg/ml of BSA-MAA from approximately 1 to 3 h. This activity subsequently begins to decrease by 4 to 6 h, with a return to baseline unstimulated kinase activity levels by 24 h. No activation of cyclic AMP-dependent protein kinase (PKA) or cyclic GMP-dependent protein kinase (PKG) was observed in BSA-MAA-treated BECs. The MAA adduct activation of PKC was followed by a fourfold to tenfold greater release of IL-8 over that observed for both BECs exposed to media only and BSA control-treated BECs. Protein kinase C activation and IL-8 release were blocked by pretreating BECs with 1 microM calphostin C or 100 nM of the PKC alpha-specific inhibitor, Go 6976. Isoform-specific inhibitors to PKC beta, PKC delta, and PKC zeta failed to inhibit completely MAA adduct-stimulated PKC or IL-8 release. Results of these studies indicate that metabolites derived from ethanol and cigarette smoke, such as acetaldehyde and malondialdehyde, form adducts that stimulate airway epithelial cell PKC alpha-mediated release of promigratory cytokines.

Acetaldehyde↗

PubMed2001

Chronic ethanol downregulates PKA activation and ciliary beating in bovine bronchial epithelial cells.

Previously, we reported that ethanol (EtOH) stimulates a rapid increase in ciliary beat frequency (CBF) of bovine bronchial epithelial cells (BBEC). Agents activating cAMP-dependent protein kinase (PKA) also stimulate CBF. EtOH stimulates BBEC CBF through cyclic nucleotide kinase activation. However, EtOH-stimulated CBF is maximal by 1 h and subsides by 6 h, returning to baseline by 24 h. We hypothesized that the loss of EtOH-stimulated CBF was a result of downregulation of PKA activity. To determine the PKA activation state in response to EtOH, ciliated BBEC were stimulated for 0--72 h with various concentrations of EtOH and assayed for PKA. EtOH (100 mM) treatment of the cells for 1 h increased PKA activity threefold over unstimulated controls. PKA activity decreased with increasing time from 6 to 24 h. When BBEC were preincubated with 100 mM EtOH for 24 h, the stimulation of PKA by isoproterenol or 8-bromo-cAMP was abrogated. EtOH desensitizes BBEC to PKA-activating agents, suggesting that EtOH rapidly stimulates, whereas long-term EtOH downregulates, CBF via PKA in BBEC.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Acetaldehyde-stimulated PKC activity in airway epithelial cells treated with smoke extract from normal and smokeless cigarettes.

Previously, we have found that acetaldehyde, a volatile component of cigarette smoke, stimulates the protein kinase C (PKC) pathway and inhibits ciliary motility. A "smokeless" cigarette (Eclipse) now exists in which most of the tobacco is not burned, reducing the pyrolyzed components in the extract. We hypothesized that acetaldehyde is a component of cigarette smoke that activates PKC in the airway epithelial cell, and therefore the Eclipse cigarette would not activate epithelial cell PKC. In this study, bovine bronchial epithelial cells (BBEC) were incubated with cigarette smoke extract (CSE) or Eclipse smoke extract (ESE). We found that PKC activity was significantly higher in cells exposed to 5% CSE than cells exposed to 5% ESE or media. When acetaldehyde levels of both extracts were measured by gas chromatography, CSE was found to have 15-20 times greater concentration (microM) of acetaldehyde than ESE. When BBEC were treated with 5% CSE, ciliary beating was further decreased from baseline levels. This decrease in ciliary beating was not observed in cells treated with ESE, suggesting that acetaldehyde contained in CSE slows cilia. These results suggest that volatile components such as acetaldehyde in cigarette smoke may inhibit ciliary motility via a PKC-dependent mechanism.

Animals↗

PubMed1999

Thoracic complications related to bone marrow transplantation.

Although progress has been made in the diagnosis and management of respiratory complications after BMT, such complications are still frequent and are a major cause of morbidity and mortality. The use of CMV-negative marrow and blood products, surveillance bronchoscopies, and prophylactic use of antivirals have significantly reduced the incidence of CMV pneumonia. DNA amplification techniques have allowed earlier detection of viral respiratory infections, and early detection of localized invasive aspergillosis can improve survival with lung resection and antifungal therapy. Finally, consideration for open lung biopsy should include the patient's degree of preoperative respiratory impairment, because this may relate to early postoperative survival.

Bone Marrow Transplantation↗

PubMed1999

Nitric oxide-dependent ethanol stimulation of ciliary motility is linked to cAMP-dependent protein kinase (PKA) activation in bovine bronchial epithelium.

BACKGROUND: The first line of protection in the lung from the outside environment is provided by the mucociliary apparatus, which continually clears the airways of inhaled microorganisms, dust, and debris. Because alcohol is known to impair airway host defenses, we have examined the effects of ethanol on mucociliary function. In earlier studies, we found that ethanol rapidly and transiently stimulates ciliary motility through a nitric oxide-dependent mechanism. Because many agonists stimulate ciliary motility through activation of cyclic nucleotide-dependent protein kinases, we hypothesized that ethanol stimulates ciliary motility by activating protein kinases. METHODS: Protein kinase activity and ciliary beat frequency (CBF) were assayed in primary cultures of bovine bronchial epithelial cells after exposure to ethanol. RESULTS: Ethanol markedly activated cyclic adenosine monophosphate (cAMP)-dependent protein kinase [protein kinase A (PKA)] at biologically relevant concentrations (20-100 mM), with activation detectable after 15 min and persisting up to 4 hr. Ethanol's PKA activation was blocked by nitric oxide synthase inhibitors, indicating a nitric oxide-dependent pathway, and was also specifically blocked by PKA inhibitors. Ethanol did not directly activate cyclic guanosine monophosphate (cGMP)-dependent protein kinase [protein kinase G (PKG)] in bovine bronchial epithelial cells, but inhibitors of PKG attenuated PKA activation, suggesting a link between PKA activation and PKG activation during ethanol exposure. CBF increased in parallel to PKA activation, suggesting tight coupling between stimulated CBF and PKA activation. CONCLUSION: We conclude that ethanol stimulates CBF through activating PKA in bovine bronchial epithelial cells and we suggest a cooperative mechanism involving PKA and nitric oxide.

Animals↗

PubMed1998

Regulation of ciliary beat frequency by both PKA and PKG in bovine airway epithelial cells.

Ciliary beating is required for the maintenance of lung mucociliary transport. We investigated the role of cyclic nucleotide-dependent protein kinases in stimulating ciliary beat frequency (CBF) in bovine bronchial epithelial cells (BBECs). cAMP-dependent protein kinase (PKA) activity and cGMP-dependent protein kinase (PKG) activity were distinguished after DEAE-Sephacel chromatography of BBEC extracts. cAMP levels and PKA activity are increased in BBECs stimulated with 0.01-1 mM isoproterenol, with a corresponding increase in CBF. cGMP levels and PKG activity are increased in BBECs stimulated with 0.1-10 microM sodium nitroprusside, with a corresponding increase in CBF. Direct protein kinase-activating analogs of cAMP and cGMP (dibutyryl cAMP and 8-bromo-cGMP, respectively) also activate their specific kinases and stimulate CBF. Preincubation of BBECs with inhibitors of PKA or PKG [KT-5720 or Rp-8-(p-chlorophenylthio)-guanosine 3',5'-cyclic monophosphothioate] results in the inhibition of specific kinase activity as well as in the inhibition of CBF. These studies suggest that the activation of either PKA or PKG can lead to the stimulation of CBF in bovine airway epithelium.

Animals↗

PubMed1997

Human lung mononuclear cells induce nitric oxide synthase in murine airway epithelial cells in vitro: role of TNFalpha and IL-1beta.

Nitric oxide (NO) is a gas released by the airway epithelium, but the mechanism regulating NO release is unclear. We hypothesized that lung mononuclear cell release of tumor necrosis factor alpha (TNF) and interleukin-1beta (IL-1) would induce epithelial cells to release NO. Lung mononuclear cells were obtained from seven normal volunteers by bronchoalveolar lavage and cultured with Escherichia coli lipopolysaccharide for 24 h. The mononuclear cell culture-conditioned media (M-CM) were then applied to cultures of the murine lung epithelial cell line, LA-4. Nitrite and nitrite + nitrate concentrations were 0.9 +/- 0.1 and 11.8 +/- 2.4 microM in the M-CM. Culturing LA-4 cells line with the M-CM (1:10 dilution) resulted in a marked and time-dependent increase in nitrite or nitrite + nitrate compared with LA-4 cells cultured in media alone (2.4 +/- 0.5 versus 0.9 +/- 0.1 microm and 16.6 +/- 0.6 versus 11.8 +/- 2.4 microM after 24 h). Antibodies to TNF and/or IL-1 significantly reduced the nitrite or nitrite + nitrate concentrations and the concentrations of TNF and IL-1 in the M-CM correlated with nitrite concentrations in the LA-4 culture supernatant fluids (r2 = 0.848 and 0.956). Inducible nitric oxide synthase (iNOS) protein and mRNA examined by immunohistochemistry and Northern blot analysis revealed a marked elevation in the cells cultured with the M-CM which was significantly reduced by TNF and IL-1 antibodies. These data demonstrate that mononuclear cells can stimulate LA-4 cells to express iNOS by releasing TNF and IL-1.

Animals↗

PubMed1996

Measurement of exhaled nitric oxide by three different techniques.

The purpose of the study was to compare exhaled nitric oxide (NO) determined by three techniques. Ninety-one subjects performed a slow vital capacity maneuver: (1) through the mouth directly into a NO chemiluminescence analyzer (peak oral NO), (2) through the mouth into a collection bag (mean oral NO), and (3) through the nose into a collection bag (mean nasal NO). Peak oral NO was higher in patients with asthma (n = 18, 174.2 +/- 27.0 ppb), but lower in smokers (n = 36, 39.6 +/- 4.8 ppb) compared with nonsmoking control subjects (n = 23, 105.5 +/- 8.4 ppb, p < 0.05 both comparisons). Mean oral NO levels were significantly lower than peak oral NO levels (p < 0.05), but still higher in patients with asthma in comparison with nonsmoking healthy control subjects and asymptomatic smokers (27.2 +/- 3.5 versus 14.5 +/- 1.1 and 7.3 +/- 0.7 ppb, respectively, p < 0.05). In contrast, there was no significant difference in mean nasal NO levels between the three groups. Peak oral NO and mean oral NO levels correlated (r = 0.772, p < 0.0001). Determination of exhaled oral NO levels is qualitatively independent of the technique used, but nasal exhalation may affect NO determination in conditions associated with airway inflammation.

Adult↗

PubMed1996

UNMC: taking steps toward better healthcare.

To be successful, the system will need to be easily modified. Do not dissolve the tailoring team when the clinician screens are "done." Anticipate constant change in how patients are cared for and plan to change the system accordingly. Communicate with the vendor so that the company understands your changing needs and so you can keep current with new functionality. Above all, listen to your clinician users--"The customer is always right."

Academic Medical Centers↗

PubMed1996

Cardiopulmonary function and autologous bone marrow transplantation: results and predictive value for respiratory failure and mortality. The University of Nebraska Medical Center Bone Marrow Transplantation Pulmonary Study Group.

Cardiopulmonary complications are a major cause of morbidity and mortality in patients undergoing high-dose therapy with stem cell transplant support. Since exercise tolerance testing (ETT) assesses the cardiopulmonary reserve of an individual, we hypothesized that ETT performed prior to transplant would predict respiratory failure and mortality and would be a superior predictor over resting cardiopulmonary function tests. We performed a retrospective study of 191 lymphoma patients who underwent ETT prior to transplant between 1 June 1990 and 31 December 1992 and compared the results of ETT with resting pulmonary function tests (PFT) and resting cardiac ejection fraction (EF). ETT revealed that cardiac, pulmonary and combined cardiopulmonary limitation were observed in 31, 20 and 16% of the patients, respectively, with a gas diffusion-type limitation being the most common exercise limitation. Resting PFT were abnormal in 58% of patients with a diffusion defect being the most common abnormality. Low EF was observed in 6.8% of patients. Twelve patients eventually required mechanical ventilation post-transplant with only the resting diffusion PFT predictive of this complication. There were five early deaths that were attributable to respiratory failure and neither resting nor ETT studies were predictive of these deaths. ETT and EF performed prior to transplant in lymphoma patients undergoing autologous transplant do not predict for either respiratory failure or short-term mortality. Our findings may be due to the rather low incidence of respiratory failure (6.3%) and low early mortality from cardiopulmonary complications (2.6%) seen in our patient population.

Adolescent↗

PubMed1995

Phenol sulfotransferase activities and localization in human nasal polyp epithelium.

Nasal polyp epithelia, which exhibit a wide variation in epithelial cell morphologies, were tested for phenol sulfotransferase (PST) enzymes. Immunohistology revealed little or no detectable PST antigen in normal ciliated pseudostratified epithelia or in simple squamous metaplastic epithelia; however, intense expression was observed in regions of non-ciliated epithelial cell hyperplasia and in squamous epithelial cells overlying such hyperplastic sites. Western blots confirmed the presence of both P-PST (32 kDa) and M-PST (34 kDa) in the tissue extracts. Bimodal distribution of PST activity as a function of 4-nitrophenol concentration was consistent with expression of these two PST isoforms. These results indicate dynamic and epithelial differentiation-dependent expression of human PSTs in the nasal mucosa and suggest that these sulfotransferases can be modulated within human airways in vivo.

Arylsulfotransferase↗

PubMed1995

Ethanol stimulates apparent nitric oxide-dependent ciliary beat frequency in bovine airway epithelial cells.

The mucociliary apparatus of the lung provides an important host-defense function by clearing the upper airway of inhaled particles and infectious microorganisms. Because lung host defenses are impaired in alcoholics, we hypothesized that ethanol would decrease ciliary motility in airway epithelium. Ciliary beat frequency (CBF) was measured by videomicroscopy in primary cultures of ciliated bovine bronchial epithelial cells (BBECs). Ethanol rapidly stimulated ciliary motility in a time-dependent fashion with concentrations as low as 10 mM. No detectable decreases in ciliary motility were noted until ethanol concentrations exceeded 1,000 mM. Because many substances stimulate ciliary motility by releasing nitric oxide (NO) via upregulation of nitric oxide synthase (NOS), we preincubated ciliated BBECs with a stereospecific NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA). L-NMMA completely blocked ethanol-induced stimulation of CBF, which could be subsequently restored by adding either L-arginine or sodium nitroprusside, which is a direct NO donor. These results indicate that ethanol, at clinically relevant concentrations, stimulates the release of NO by airway epithelium that upregulates ciliary motility. The rapidity of this response suggests upregulation of the constitutive NOS, known to be present in airway epithelium, and may explain the increases in mucociliary clearance observed in previous studies of ethanol ingestion in animals and in humans. These data also suggest a novel signal transduction pathway, the NO/NOS system, by which ethanol may exert some of its diverse biologic effects.

Alcohols↗

PubMed1995

Effects of cigarette smoke extract on bovine bronchial epithelial cell attachment and migration.

The repair of injured epithelium involves a complex interaction between epithelial cells and the underlying extracellular matrix. We studied the effects of sublethal concentrations of cigarette smoke extract (CSE) and two volatile components of cigarette smoke, acetaldehyde and acrolein, on bovine bronchial epithelial cell (BBEC) attachment and migration in vitro. After short-term exposure (2 and 6 h) to CSE, BBEC attachment to fibronectin-coated dishes was decreased, and migration to fibronectin was unchanged. After a longer period of exposure, 24 h, attachment was increased and migration was unchanged. Exposure to a peptide containing the amino acid sequence arginine-glycine-aspartic acid (RGD) reduced attachment equally well for control and smoke-exposed cells. BBEC sheet migration was reduced over 72 h after exposure to CSE. Acrolein reduced BBEC migration to fibronectin but had no effect on attachment. Acetaldehyde had no effect on either attachment or migration. We conclude that exposure to CSE has important effects on bronchial epithelial cell migration and attachment, and that these effects change over time.

Acetaldehyde↗

PubMed1995

TNF-alpha and IL-1 beta upregulate nitric oxide-dependent ciliary motility in bovine airway epithelium.

Airway epithelial cells can be modulated by cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (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 h with bovine alveolar macrophage-conditioned medium (AM-CM). Exposure to AM-CM resulted in a delayed (> or = 2 h) increase in CBF that was maximal after 24 h exposure (13.70 +/- 0.43 for AM-CM vs. 9.44 +/- 0.24 Hz for medium; 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. Preincubation 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 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, an NOS substrate, or sodium nitroprusside, an NO donor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗