Mycobacterium fortuitum induces A20 expression that impairs macrophage inflammatory responses
| Autor: | Hye-Mi Lee, Jin Kyung Kim, Kyung Mok Sohn, Gippeum Joy Lee, Eun-Kyeong Jo, Tae Sung Kim |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_treatment Mycobacterium Infections Nontuberculous Inflammation Bone Marrow Cells Microbiology Proinflammatory cytokine Cell Line 03 medical and health sciences chemistry.chemical_compound Mice medicine Immunology and Allergy Animals RNA Small Interfering Tumor Necrosis Factor alpha-Induced Protein 3 General Immunology and Microbiology biology Interleukin-6 Mycobacterium fortuitum Tumor Necrosis Factor-alpha Macrophages Intracellular Signaling Peptides and Proteins Transcription Factor RelA NF-κB General Medicine biology.organism_classification Toll-Like Receptor 2 Mice Inbred C57BL TLR2 Cysteine Endopeptidases 030104 developmental biology Infectious Diseases Cytokine chemistry Myeloid Differentiation Factor 88 Tumor necrosis factor alpha RNA Interference Signal transduction medicine.symptom |
| Zdroj: | Pathogens and disease. 74(3) |
| ISSN: | 2049-632X |
| Popis: | Mycobacterium fortuitum is a rapidly growing mycobacterium that has been regarded as an etiological agent of a variety of human infections. However, little is known about the host inflammatory responses and the molecular mechanisms by which MF-induced inflammation is regulated in macrophages. In this study, we report that MF infection leads to the induction of an anti-inflammatory molecule, A20 (also known as TNFAIP3), which is essential for the regulation of MF-induced inflammatory responses in murine bone marrow-derived macrophages (BMDMs). MF triggered the expression of tumor necrosis factor-α and interleukin-6 in BMDMs through signaling of the Toll-like receptor 2 (TLR2)-myeloid differentiation primary response gene 88. Additionally, MF rapidly induced the expression of A20, which inhibited proinflammatory cytokine expression and nuclear factor (NF)-κB reporter gene activities in BMDMs. Notably, MF-induced activation of NF-κB signaling was required for A20 expression and proinflammatory responses in BMDMs. Furthermore, the rough morphotype of the MF clinical strain induced a higher level of proinflammatory signaling activation, but less A20 induction in BMDMs, compared to the smooth morphotype. Taken together, these results suggest that MF-induced activation of host proinflammatory responses is negatively regulated through TLR2-dependent A20 expression. |
| Databáze: | OpenAIRE |
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