مقاله جدید( 2012)

Glutamine Suppresses Airway Neutrophilia by Blocking Cytosolic Phospholipase A2 via an Induction of MAPK Phosphatase-1

1. Chang-Hoon Lee*,
2. Hae-Kyoung Kim*,
3. June-Mo Kim*,
4. Otgonzaya Ayush*,
5. Suhn-Young Im†,
6. Dae-Kyu Oh‡,1 and
7. Hern-Ku Lee*,1

1. ^*Department of Immunology, Chonbuk National University Medical School, Jeonju, Chonbuk 561-182, Republic of Korea;
2. ^†Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea; and
3. ^‡Department of Preventive Medicine, Gachon University of Medicine and Science, Incheon 406-799, Republic of Korea

1. Address correspondence and reprint requests to Dr. Hern-Ku Lee, Department of Immunology, Chonbuk National University Medical School, Jeonju, Chonbuk 561-182, Republic of Korea. E-mail address: [e-mail]

1. ↵1 D.-K.O. and H.-K.L. contributed equally to this work.

Abstract

Neutrophils are inflammatory cells that may contribute in a crucial way to the pathophysiology of steroid-resistant severe asthma. We previously reported that the nonessential amino acid l-glutamine (Gln) suppressed the recruitment of neutrophils into the airway in a murine model of asthma. In this study, we investigated the mechanisms by which Gln exerts beneficial effects in airway neutrophilia. We used the model we previously developed, which is suitable for examining sequential early asthmatic events, including neutrophil infiltration. Gln suppressed airway neutrophilia in a CXC chemokine-independent way. Airway neutrophilia was associated with cytosolic phospholipase A₂ (cPLA₂) and 5-lipoxygenase (5-LO) activities. p38 MAPK, the upstream pathway of cPLA₂ and 5-LO, played a key role in inducing airway neutrophilia. Gln inhibited not only the phosphorylation of cPLA₂ and p38 MAPK but also leukotriene B₄ levels in the airways. Gln induced the early induction of MAPK phosphatase-1 (MKP-1) protein, a negative regulator of p38. MKP-1 small interfering RNA abrogated all the effects of Gln. Our results suggest that pathways involving p38/cPLA₂/5-LO have a major role in airway neutrophilia. Gln suppresses airway neutrophilia via inhibiting p38 MAPK and its downstream pathways in an MKP-1–dependent way, which may provide a novel therapeutic strategy for pulmonary neutrophilic inflammatory diseases.