| First Author | Ohto-Ozaki H | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 8 | Pages | 2033-2042 |
| PubMed ID | 32144162 | Mgi Jnum | J:287108 |
| Mgi Id | MGI:6406189 | Doi | 10.4049/jimmunol.1900315 |
| Citation | Ohto-Ozaki H, et al. (2020) Induction of IkappaBzeta Augments Cytokine and Chemokine Production by IL-33 in Mast Cells. J Immunol 204(8):2033-2042 |
| abstractText | IkappaBzeta (encoded by the Nfkbiz) is a member of the nuclear IkappaB family, which is involved in the expression of secondary response genes based on signals from TLR or IL-1R. ST2L, an IL-33R, is a member of the IL-1R family and abundantly expressed in tissue-resident immune cells, such as mast cells and innate lymphoid cells; however, its downstream signaling pathway remains unelucidated. In this study, we examined the role of IkappaBzeta in ST2L-mediated cytokine and chemokine production in mast cells. Murine bone marrow cells were differentiated ex vivo into bone marrow-derived mast cells (BMMCs). The treatment of BMMCs with IL-33 transiently induced robust IkappaBzeta expression. Of the 40 cytokines and chemokines examined using a cytokine and chemokine array, the concentrations of IL-6, IL-13, CCL2, CCL3, and TNF-alpha in the supernatant were augmented by IL-33. The deletion of IkappaBzeta in BMMCs resulted in a significant reduction of the production of these mediators and the expression of their mRNA. NF-kappaB p50 but not p65 translocated to the nucleus by IL-33 and was not affected by the deletion of IkappaBzeta. However, induction of IkappaBzeta and the resultant cytokine and chemokine productions were significantly inhibited by pretreatment with an NF-kappaB inhibitor. The deletion of IkappaBzeta did not affect the phosphorylation of ERK, p38 MAPK, or JNK by IL-33, and the treatment with inhibitors of these mitogen-activated kinases failed to abolish the expression of Nfkbiz Our findings suggest that IkappaBzeta augments IL-33-dependent cytokine and chemokine production in BMMCs through the action of NF-kappaB. |
