Allergic lung responses are increased in prostaglandin H synthase–deficient mice
Stephen H. Gavett,Sharon L. Madison,Patricia C. Chulada,Paula E. Scarborough,Wei Qu,James E. Boyle,Howard F. Tiano,Christopher A. Lee,Robert Langenbach,Victor L. Roggli,Darryl C. Zeldin +10 more
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TLDR
PGHS-1 is the predominant enzyme that biosynthesizes PGE(2) in the normal mouse lung and products limit allergic lung inflammation and IgE secretion and promote normal lung function, and airway inflammation can be dissociated from the development of airway hyperresponsiveness in PGHS-2(-/-) mice.Abstract:
To investigate the function of prostaglandin H synthase-1 and synthase-2 (PGHS-1 and PGHS-2) in the normal lung and in allergic lung responses, we examined allergen-induced pulmonary inflammation and airway hyperresponsiveness in wild-type mice and in PGHS-1(-/-) and PGHS-2(-/-) mice. Among nonimmunized saline-exposed groups, we found no significant differences in lung function or histopathology, although PGE(2) was dramatically reduced in bronchoalveolar lavage (BAL) fluid from PGHS-1(-/-) mice, relative to wild-type or PGHS-2(-/-) mice. After ovalbumin sensitization and challenge, lung inflammatory indices (BAL cells, proteins, IgE, lung histopathology) were significantly greater in PGHS-1(-/-) mice compared with PGHS-2(-/-) mice, and both were far greater than in wild-type mice, as illustrated by the ratio of eosinophils in BAL fluid (8:5:1, respectively). Both allergic PGHS-1(-/-) and PGHS-2(-/-) mice exhibited decreased baseline respiratory system compliance, whereas only allergic PGHS-1(-/-) mice showed increased baseline resistance and responsiveness to methacholine. Ovalbumin exposure caused a modest increase in lung PGHS-2 protein and a corresponding increase in BAL fluid PGE(2) in wild-type mice. We conclude that (a) PGHS-1 is the predominant enzyme that biosynthesizes PGE(2) in the normal mouse lung; (b) PGHS-1 and PGHS-2 products limit allergic lung inflammation and IgE secretion and promote normal lung function; and (c) airway inflammation can be dissociated from the development of airway hyperresponsiveness in PGHS-2(-/-) mice.read more
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References
More filters
Journal ArticleDOI
Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration.
Robert Langenbach,Scott G. Morham,Howard F. Tiano,Charles D. Loftin,Burhan I. Ghanayem,Patricia C. Chulada,Joel F. Mahler,Christopher A. Lee,Eugenia H. Goulding,Kimberly D. Kluckman,Hyung Suk Kim,Oliver Smithies +11 more
TL;DR: COX-1-deficient mice provide a useful model to distinguish the physiological roles of COx-1 and COX-3, the target enzymes for the widely used nonsteroidal anti-inflammatory drugs.
Journal ArticleDOI
Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse
Scott G. Morham,Robert Langenbach,Charles D. Loftin,Howard F. Tiano,Nectarios Vouloumanos,J. Charles Jennette,Joel F. Mahler,Kimberly D. Kluckman,Aric Ledford,Christopher A. Lee,Oliver Smithies +10 more
TL;DR: Mice lacking COX-2 have normal inflammatory responses to treatments with tetradecanoyl phorbol acetate or with arachidonic acid, however, they develop severe nephropathy and are susceptible to peritonitis.
Journal ArticleDOI
Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II.
Joseph E. Dinchuk,Bruce D. Car,Richard J. Focht,Jennifer J. Johnston,Bruce D. Jaffee,Maryanne B. Covington,Nancy R. Contel,Vicki M. Eng,Robert Collins,P. M. Czerniak,Stewart A. Gorry,James M. Trzaskos +11 more
TL;DR: An animal model of COX-2 deficiency that was generated by gene targeting failed to alter inflammatory responses in several standard models, but striking mitigation of endotoxin-induced hepatocellular cytotoxicity was observed.
Journal ArticleDOI
IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2
J Pène,Françoise Rousset,Francine Brière,I Chrétien,J Y Bonnefoy,Hergen Spits,Takashi Yokota,Naoko Arai,Ken-ichi Arai,Jacques Banchereau +9 more
TL;DR: The IL-4-induced IgE production by B cells required T cells and monocytes but was specifically inhibited by an anti-IL-4 antiserum indicating that, although IL- 4 acts indirectly, it is responsible for the induction of IgE synthesis.
Journal ArticleDOI
Treatment of Asthma with Drugs Modifying the Leukotriene Pathway
TL;DR: In 1979 and 1980, the chemical structures of the material previously known as slow-reacting substance of anaphylaxis were elucidated as 5(S)- hydroxy- 6(R)-glutathionyl- 7,9-trans-11,14- cis - eico- satetraenoic acid1 and its cysteinyl-glycyl and cysteiny congener.