Treatment of established TH2 cells with 4μ8c, an inhibitor of IRE1α, blocks IL-5 but not IL-4 secretion
| Autor: | Karissa Hodge, Kyeorda Kemp, Cheyanne Youngblood, Cody Poe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine medicine.medical_treatment T cell Immunology 4μ8c Protein Serine-Threonine Kinases Flow cytometry Cell Line 03 medical and health sciences Mice 0302 clinical medicine Th2 Cells Endoribonucleases medicine Animals Humans Secretion RNA Processing Post-Transcriptional Interleukin 5 Interleukin 4 IL-5 medicine.diagnostic_test Chemistry Cell Differentiation IRE1α Molecular biology 3. Good health TH2 030104 developmental biology Cytokine medicine.anatomical_structure Cell culture Unfolded protein response Cytokines Protein secretion Interleukin-4 Interleukin-5 lcsh:RC581-607 Hymecromone 030215 immunology Research Article |
| Zdroj: | BMC Immunology BMC Immunology, Vol 20, Iss 1, Pp 1-10 (2019) |
| ISSN: | 1471-2172 |
| Popis: | Background T cell activation induces ER stress and upregulates Inositol Requiring Enzyme 1 alpha (IRE1α), an activator of the unfolded protein response (UPR) pathway. Inhibition of IRE1α RNase activity in activated CD4+ splenocytes from naïve mice, via treatment of the cells with the commercially available drug 4μ8c upon activation, results in the reduction of the secretion of proteins IL-5, IL-4, and IL-13. Prior to this work, it was unknown if 4μ8c could inhibit TH2 cytokines in established TH2 cells, cells that are crucial in promoting disease in severe asthma. Results Treatment of a mouse T helper (TH)2 cell line and differentiated human TH2 cells with 4μ8c resulted in inhibition of IL-5, but not IL-4, as measured by ELISA. The reduced cytokine expression was not due to differences in mRNA stability or mRNA levels; it appears to be due to a defect in secretion, as the cells produce cytokines IL-5 as measured by flow cytometry and western blot. Conclusion These data suggest that the inhibition of IL-5 was due to post-translational processes. IL-5 promotes chronic, inflammatory asthma, and 4μ8c blocks its expression in T cells in vitro. Future studies will determine if 4μ8c treatment can ameliorate the effects of the cytokine IL-5 in a disease model. Electronic supplementary material The online version of this article (10.1186/s12865-018-0283-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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