Lactic Acid Suppresses IL-33–Mediated Mast Cell Inflammatory Responses via Hypoxia-Inducible Factor-1α–Dependent miR-155 Suppression
| Autor: | Marcela T. Taruselli, John J. Ryan, Jamie Josephine Avila McLeod, Andrew J. Spence, Amina Abdul Qayum, Victor S. Ndaw, Bianca Baker, Heather L. Caslin, Alena P. Chumanevich, Brian O. Barnstein, Elizabeth Motunrayo Kolawole, Daniel Abebayehu, Anuya Paranjape, Carole A. Oskeritzian, Scott A. Sell |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine MAPK/ERK pathway medicine.medical_specialty Chemokine medicine.medical_treatment p38 mitogen-activated protein kinases Immunology Inflammation Biology Article Mice Structure-Activity Relationship 03 medical and health sciences Internal medicine medicine Animals Humans Immunology and Allergy Lactic Acid Mast Cells Cells Cultured Dose-Response Relationship Drug Hypoxia-Inducible Factor 1 alpha Subunit Interleukin-33 Mast cell Cell biology Mice Inbred C57BL Interleukin 33 MicroRNAs 030104 developmental biology Endocrinology medicine.anatomical_structure Cytokine Hypoxia-inducible factors biology.protein Female medicine.symptom |
| Zdroj: | The Journal of Immunology. 197:2909-2917 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1600651 |
| Popis: | Lactic acid (LA) is present in tumors, asthma, and wound healing, environments with elevated IL-33 and mast cell infiltration. Although IL-33 is a potent mast cell activator, how LA affects IL-33–mediated mast cell function is unknown. To investigate this, mouse bone marrow–derived mast cells were cultured with or without LA and activated with IL-33. LA reduced IL-33–mediated cytokine and chemokine production. Using inhibitors for monocarboxylate transporters (MCT) or replacing LA with sodium lactate revealed that LA effects are MCT-1– and pH-dependent. LA selectively altered IL-33 signaling, suppressing TGF-β–activated kinase-1, JNK, ERK, and NF-κB phosphorylation, but not p38 phosphorylation. LA effects in other contexts have been linked to hypoxia-inducible factor (HIF)-1α, which was enhanced in bone marrow–derived mast cells treated with LA. Because HIF-1α has been shown to regulate the microRNA miR-155 in other systems, LA effects on miR-155-5p and miR-155-3p species were measured. In fact, LA selectively suppressed miR-155-5p in an HIF-1α–dependent manner. Moreover, overexpressing miR-155-5p, but not miR-155-3p, abolished LA effects on IL-33–induced cytokine production. These in vitro effects of reducing cytokines were consistent in vivo, because LA injected i.p. into C57BL/6 mice suppressed IL-33–induced plasma cytokine levels. Lastly, IL-33 effects on primary human mast cells were suppressed by LA in an MCT-dependent manner. Our data demonstrate that LA, present in inflammatory and malignant microenvironments, can alter mast cell behavior to suppress inflammation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|