Pneumocystisstimulates MCP-1 production by alveolar epithelial cells through a JNK-dependent mechanism
| Autor: | Sanjay B. Maggirwar, Francis Gigliotti, Jing Wang, Samir P. Bhagwat, Terry W. Wright |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Pulmonary and Respiratory Medicine
MAPK/ERK pathway beta-Glucans MAP Kinase Signaling System Physiology p38 mitogen-activated protein kinases Chemokine CXCL2 Gene Expression Inflammation Mice SCID Respiratory Mucosa Lung injury Biology p38 Mitogen-Activated Protein Kinases Proinflammatory cytokine Mice Immune system Physiology (medical) medicine Animals Cells Cultured Chemokine CCL2 Monocyte JNK Mitogen-Activated Protein Kinases NF-kappa B Epithelial Cells Cell Biology respiratory system respiratory tract diseases Mice Inbred C57BL Pneumocystis Infections Pulmonary Alveoli Disease Models Animal medicine.anatomical_structure Pneumocystis carinii Immunology Cancer research Chemokines medicine.symptom |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 292:L1495-L1505 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00452.2006 |
| Popis: | Pneumocystis carinii is an opportunistic fungal pathogen that causes pneumonia (PCP) in immunocompromised individuals. Recent studies have demonstrated that the host's immune response is clearly responsible for the majority of the pathophysiological changes associated with PCP. P. carinii interacts closely with alveolar epithelial cells (AECs); however, the nature and pathological consequences of the epithelial response remain poorly defined. Monocyte chemotactic protein-1 (MCP-1) is involved in lung inflammation, immunity, and epithelial repair and is upregulated during PCP. To determine whether AECs are an important source of MCP-1 in the P. carinii-infected lung, in vivo and in vitro studies were performed. In situ hybridization showed that MCP-1 mRNA was localized to cells with morphological characteristics of AECs in the lungs of infected mice. In vitro studies demonstrated that P. carinii stimulated a time- and dose-dependent MCP-1 response in primary murine type II cells that was preceded by JNK activation. Pharmacological inhibition of JNK nearly abolished P. carinii-stimulated MCP-1 production, while ERK, p38 MAPK, and TNF receptor signaling were not required. Furthermore, delivery of a JNK inhibitory peptide specifically to pulmonary epithelial cells using a recombinant adenovirus vector blocked the early lung MCP-1 response following intratracheal instillation of infectious P. carinii. JNK inhibition did not affect P. carinii-stimulated production of macrophage inflammatory protein-2 in vitro or in vivo, indicating that multiple signaling pathways are activated in P. carinii-stimulated AECs. These data demonstrate that AECs respond to P. carinii in a proinflammatory manner that may contribute to the generation of immune-mediated lung injury. |
| Databáze: | OpenAIRE |
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