Prostaglandin E2-Mediated Impairment of Innate Immune Response to A(H1N1)pdm09 Infection in Diet-Induced Obese Mice Could Be Restored by Paracetamol
| Autor: | Leonardi Gozali, Anna J. X. Zhang, Ivan Hung, Houshun Zhu, Chuangen Li, Hin Chu, Can Li, Andrew Chak-Yiu Lee, Kwok-Yung Yuen, Yanxia Chen, Kelvin K. W. To |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Chemokine medicine.medical_treatment Mice Obese Systemic inflammation Dinoprostone Proinflammatory cytokine 03 medical and health sciences Influenza A Virus H1N1 Subtype 0302 clinical medicine Immune system Orthomyxoviridae Infections Internal medicine medicine Animals Immunologic Factors Immunology and Allergy 030212 general & internal medicine Lung Acetaminophen Innate immune system biology business.industry nutritional and metabolic diseases Immunity Innate Mice Inbred C57BL Treatment Outcome 030104 developmental biology Infectious Diseases Endocrinology Cytokine biology.protein Cytokines Female medicine.symptom business Diet-induced obese hormones hormone substitutes and hormone antagonists Prostaglandin E |
| Zdroj: | The Journal of Infectious Diseases. 219:795-807 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jiy527 |
| Popis: | BACKGROUND Obesity is associated with increased severity of influenza infection. However, the underlying mechanism is largely unknown. METHODS We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus. RESULTS The lungs of DIO mice were heavily affected by obesity-associated chronic systemic inflammation with a significant increase in inflammatory cytokines/chemokines. Concurrently, lipid immune mediator prostaglandin E2 (PGE2) was also significantly elevated in DIO mice. However, the DIO mice mounted a blunted and delayed upregulation of mRNA and protein concentrations of interferon-β and inflammatory cytokines/chemokines upon A(H1N1)pdm09 virus (H1N1/415742Md) challenge compared with those of lean mice. PGE2 concentrations were significantly higher in the lungs of DIO mice compared to that of lean mice postchallenge. Treatment with paracetamol in challenged DIO mice significantly enhanced the expression of interferon-α/β and cytokine genes at days 1 and 3 postinfection compared with that of untreated DIO mice. Furthermore, paracetamol treatment alone started 3 days before virus challenge and continued until 6 days postchallenge ameliorated the severity of a lethal H1N1/415742Md infection in DIO mice with improved survival. CONCLUSIONS Impaired innate response to influenza in DIO mice is associated with elevated PGE2, which could be restored to some degree by paracetamol treatment. |
| Databáze: | OpenAIRE |
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