Effect of endogenous nitric oxide on tumour necrosis factor-α-induced leukosequestration and IL-8 release in airways in vivo

H. P. Kuo, K. H. Hwang, H. C. Lin, C. H. Wang, L. C. Lu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Tumour necrosis factor-α (TNF-α) is implicated in the pathogenesis of many pulmonary and airway diseases. TNF-α stimulation may release interleukin-8 (IL-8) in airways mediated via an increase in intracellular oxidant stress. In the present study, we have assessed leukosequestration and IL-8 release in the airways in response to intratracheal administration of human recombinant TNF-α, and examined the modulatory role of endogenous NO by pretreatment with a NO synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME). 2. TNF-α (102-104 u) was administered intratracheally in male guinea-pigs which were anaesthetized with urethane and were ventilated artificially. TNF-α induced a time- and dose-related increase in neutrophil numbers and a concomitant increase in human IL-8 equivalent level retrieved from bronchoalveolar lavage (BAL) with the peak effect at 103 u at 6 h of TNF-α injection (late phase). Intratracheal administration of recombinant human (rh)IL-8 (0.025, 0.25, 2.5 ng) producing a similar range of human IL-8 equivalent levels in BAL as measured in our results induced neutrophil recovery in BAL fluid to a similar extent. Administration of anti-IL-8 antibody prevented the late phase of neutrophil recruitment induced by TNF-α or rhIL-8. 3. Pretreatment with L-NAME significantly enhanced the TNF-α (103 u)-induced neutrophil recruitment and human IL-8 equivalents production at 6 h, but not at 1 h of TNF-α administration (early phase). L-Arginine reversed the responses to L-NAME. Pretreatment with 0.2% DMSO (i.v.) significantly inhibited TNF-α-induced neutrophil recruitment and human IL-8 equivalents release both in the early and late phase of the responses. Pretreatment with DMSO also inhibited the enhancement effect of L-NAME on the late phase of TNF-α-induced responses. DMSO failed to modify exogenous rhIL-8-induced neutrophil recruitment. Neither L-NAME nor DMSO alone induced any significant change in neutrophil numbers or human IL-8 equivalent level in BAL fluid. 4. Neutrophil depletion by cyclophosphamide pretreatment failed to modify TNF-α-induced human IL-8 equivalent release. 5. The expression of β2-integrin, CD11b/CD18 on neutrophils was increased only in the late but not early phase of TNF-α stimulation. L-NAME failed to modify these responses. 6. In conclusion, we demonstrated that NO may be an important endogenous inhibitor of TNF-α-induced leukocyte chemotaxis via inhibition of IL-8 production. Thus, the production of NO in airway inflammatory diseases may play a negative feedback role in self-limiting the magnitude of inflammatory responses.

Original languageEnglish
Pages (from-to)103-111
Number of pages9
JournalBritish Journal of Pharmacology
Volume122
Issue number1
DOIs
Publication statusPublished - Sep 18 1997
Externally publishedYes

Fingerprint

Interleukin-8
Nitric Oxide
Tumor Necrosis Factor-alpha
NG-Nitroarginine Methyl Ester
Neutrophil Infiltration
Dimethyl Sulfoxide
Neutrophils
Bronchoalveolar Lavage Fluid
Bronchoalveolar Lavage
Leukocyte Chemotaxis
Cell Migration Inhibition
Urethane
Oxidants
Integrins
Nitric Oxide Synthase
Cyclophosphamide
Lung Diseases
Arginine
Guinea Pigs
Injections

Keywords

  • Adhesion molecule
  • Interleukin-8
  • Neutrophil
  • Nitric oxide
  • Respiratory system
  • Tumour necrosis factor-α

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of endogenous nitric oxide on tumour necrosis factor-α-induced leukosequestration and IL-8 release in airways in vivo. / Kuo, H. P.; Hwang, K. H.; Lin, H. C.; Wang, C. H.; Lu, L. C.

In: British Journal of Pharmacology, Vol. 122, No. 1, 18.09.1997, p. 103-111.

Research output: Contribution to journalArticle

@article{1fc0e5da49d549a09fa8208fe8ca8337,
title = "Effect of endogenous nitric oxide on tumour necrosis factor-α-induced leukosequestration and IL-8 release in airways in vivo",
abstract = "Tumour necrosis factor-α (TNF-α) is implicated in the pathogenesis of many pulmonary and airway diseases. TNF-α stimulation may release interleukin-8 (IL-8) in airways mediated via an increase in intracellular oxidant stress. In the present study, we have assessed leukosequestration and IL-8 release in the airways in response to intratracheal administration of human recombinant TNF-α, and examined the modulatory role of endogenous NO by pretreatment with a NO synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME). 2. TNF-α (102-104 u) was administered intratracheally in male guinea-pigs which were anaesthetized with urethane and were ventilated artificially. TNF-α induced a time- and dose-related increase in neutrophil numbers and a concomitant increase in human IL-8 equivalent level retrieved from bronchoalveolar lavage (BAL) with the peak effect at 103 u at 6 h of TNF-α injection (late phase). Intratracheal administration of recombinant human (rh)IL-8 (0.025, 0.25, 2.5 ng) producing a similar range of human IL-8 equivalent levels in BAL as measured in our results induced neutrophil recovery in BAL fluid to a similar extent. Administration of anti-IL-8 antibody prevented the late phase of neutrophil recruitment induced by TNF-α or rhIL-8. 3. Pretreatment with L-NAME significantly enhanced the TNF-α (103 u)-induced neutrophil recruitment and human IL-8 equivalents production at 6 h, but not at 1 h of TNF-α administration (early phase). L-Arginine reversed the responses to L-NAME. Pretreatment with 0.2{\%} DMSO (i.v.) significantly inhibited TNF-α-induced neutrophil recruitment and human IL-8 equivalents release both in the early and late phase of the responses. Pretreatment with DMSO also inhibited the enhancement effect of L-NAME on the late phase of TNF-α-induced responses. DMSO failed to modify exogenous rhIL-8-induced neutrophil recruitment. Neither L-NAME nor DMSO alone induced any significant change in neutrophil numbers or human IL-8 equivalent level in BAL fluid. 4. Neutrophil depletion by cyclophosphamide pretreatment failed to modify TNF-α-induced human IL-8 equivalent release. 5. The expression of β2-integrin, CD11b/CD18 on neutrophils was increased only in the late but not early phase of TNF-α stimulation. L-NAME failed to modify these responses. 6. In conclusion, we demonstrated that NO may be an important endogenous inhibitor of TNF-α-induced leukocyte chemotaxis via inhibition of IL-8 production. Thus, the production of NO in airway inflammatory diseases may play a negative feedback role in self-limiting the magnitude of inflammatory responses.",
keywords = "Adhesion molecule, Interleukin-8, Neutrophil, Nitric oxide, Respiratory system, Tumour necrosis factor-α",
author = "Kuo, {H. P.} and Hwang, {K. H.} and Lin, {H. C.} and Wang, {C. H.} and Lu, {L. C.}",
year = "1997",
month = "9",
day = "18",
doi = "10.1038/sj.bjp.0701338",
language = "English",
volume = "122",
pages = "103--111",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

TY - JOUR

T1 - Effect of endogenous nitric oxide on tumour necrosis factor-α-induced leukosequestration and IL-8 release in airways in vivo

AU - Kuo, H. P.

AU - Hwang, K. H.

AU - Lin, H. C.

AU - Wang, C. H.

AU - Lu, L. C.

PY - 1997/9/18

Y1 - 1997/9/18

N2 - Tumour necrosis factor-α (TNF-α) is implicated in the pathogenesis of many pulmonary and airway diseases. TNF-α stimulation may release interleukin-8 (IL-8) in airways mediated via an increase in intracellular oxidant stress. In the present study, we have assessed leukosequestration and IL-8 release in the airways in response to intratracheal administration of human recombinant TNF-α, and examined the modulatory role of endogenous NO by pretreatment with a NO synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME). 2. TNF-α (102-104 u) was administered intratracheally in male guinea-pigs which were anaesthetized with urethane and were ventilated artificially. TNF-α induced a time- and dose-related increase in neutrophil numbers and a concomitant increase in human IL-8 equivalent level retrieved from bronchoalveolar lavage (BAL) with the peak effect at 103 u at 6 h of TNF-α injection (late phase). Intratracheal administration of recombinant human (rh)IL-8 (0.025, 0.25, 2.5 ng) producing a similar range of human IL-8 equivalent levels in BAL as measured in our results induced neutrophil recovery in BAL fluid to a similar extent. Administration of anti-IL-8 antibody prevented the late phase of neutrophil recruitment induced by TNF-α or rhIL-8. 3. Pretreatment with L-NAME significantly enhanced the TNF-α (103 u)-induced neutrophil recruitment and human IL-8 equivalents production at 6 h, but not at 1 h of TNF-α administration (early phase). L-Arginine reversed the responses to L-NAME. Pretreatment with 0.2% DMSO (i.v.) significantly inhibited TNF-α-induced neutrophil recruitment and human IL-8 equivalents release both in the early and late phase of the responses. Pretreatment with DMSO also inhibited the enhancement effect of L-NAME on the late phase of TNF-α-induced responses. DMSO failed to modify exogenous rhIL-8-induced neutrophil recruitment. Neither L-NAME nor DMSO alone induced any significant change in neutrophil numbers or human IL-8 equivalent level in BAL fluid. 4. Neutrophil depletion by cyclophosphamide pretreatment failed to modify TNF-α-induced human IL-8 equivalent release. 5. The expression of β2-integrin, CD11b/CD18 on neutrophils was increased only in the late but not early phase of TNF-α stimulation. L-NAME failed to modify these responses. 6. In conclusion, we demonstrated that NO may be an important endogenous inhibitor of TNF-α-induced leukocyte chemotaxis via inhibition of IL-8 production. Thus, the production of NO in airway inflammatory diseases may play a negative feedback role in self-limiting the magnitude of inflammatory responses.

AB - Tumour necrosis factor-α (TNF-α) is implicated in the pathogenesis of many pulmonary and airway diseases. TNF-α stimulation may release interleukin-8 (IL-8) in airways mediated via an increase in intracellular oxidant stress. In the present study, we have assessed leukosequestration and IL-8 release in the airways in response to intratracheal administration of human recombinant TNF-α, and examined the modulatory role of endogenous NO by pretreatment with a NO synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME). 2. TNF-α (102-104 u) was administered intratracheally in male guinea-pigs which were anaesthetized with urethane and were ventilated artificially. TNF-α induced a time- and dose-related increase in neutrophil numbers and a concomitant increase in human IL-8 equivalent level retrieved from bronchoalveolar lavage (BAL) with the peak effect at 103 u at 6 h of TNF-α injection (late phase). Intratracheal administration of recombinant human (rh)IL-8 (0.025, 0.25, 2.5 ng) producing a similar range of human IL-8 equivalent levels in BAL as measured in our results induced neutrophil recovery in BAL fluid to a similar extent. Administration of anti-IL-8 antibody prevented the late phase of neutrophil recruitment induced by TNF-α or rhIL-8. 3. Pretreatment with L-NAME significantly enhanced the TNF-α (103 u)-induced neutrophil recruitment and human IL-8 equivalents production at 6 h, but not at 1 h of TNF-α administration (early phase). L-Arginine reversed the responses to L-NAME. Pretreatment with 0.2% DMSO (i.v.) significantly inhibited TNF-α-induced neutrophil recruitment and human IL-8 equivalents release both in the early and late phase of the responses. Pretreatment with DMSO also inhibited the enhancement effect of L-NAME on the late phase of TNF-α-induced responses. DMSO failed to modify exogenous rhIL-8-induced neutrophil recruitment. Neither L-NAME nor DMSO alone induced any significant change in neutrophil numbers or human IL-8 equivalent level in BAL fluid. 4. Neutrophil depletion by cyclophosphamide pretreatment failed to modify TNF-α-induced human IL-8 equivalent release. 5. The expression of β2-integrin, CD11b/CD18 on neutrophils was increased only in the late but not early phase of TNF-α stimulation. L-NAME failed to modify these responses. 6. In conclusion, we demonstrated that NO may be an important endogenous inhibitor of TNF-α-induced leukocyte chemotaxis via inhibition of IL-8 production. Thus, the production of NO in airway inflammatory diseases may play a negative feedback role in self-limiting the magnitude of inflammatory responses.

KW - Adhesion molecule

KW - Interleukin-8

KW - Neutrophil

KW - Nitric oxide

KW - Respiratory system

KW - Tumour necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=0030777322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030777322&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0701338

DO - 10.1038/sj.bjp.0701338

M3 - Article

C2 - 9298535

AN - SCOPUS:0030777322

VL - 122

SP - 103

EP - 111

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 1

ER -