TY - JOUR
T1 - TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes
AU - Sakaguchi, Taiki
AU - Okumura, Ryu
AU - Ono, Chisato
AU - Okuzaki, Daisuke
AU - Kawai, Takafumi
AU - Okochi, Yoshifumi
AU - Tanimura, Natsuko
AU - Murakami, Mari
AU - Kayama, Hisako
AU - Umemoto, Eiji
AU - Kioka, Hidetaka
AU - Ohtani, Tomohito
AU - Sakata, Yasushi
AU - Miyake, Kensuke
AU - Okamura, Yasushi
AU - Baba, Yoshihiro
AU - Takeda, Kiyoshi
N1 - Funding Information:
We thank Y. Magota for technical assistance and C. Hidaka for secretarial assistance. K.T. was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan ( JP15H02511 ), the Japan Agency for Medical Research and Development ( JP18gm1010004 ), and research funding from Ono Pharmaceutical ( J160799427 ). We thank the Edanz Group ( https://en-author-services.edanzgroup.com ) for editing a draft of this manuscript.
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/6/9
Y1 - 2020/6/9
N2 - B cells produce high amounts of cytokines and immunoglobulins in response to lipopolysaccharide (LPS) stimulation. Calcium signaling cascades are critically involved in cytokine production of T cells, and the cytosolic calcium concentration is regulated by calcium-activated monovalent cation channels (CAMs). Calcium signaling is also implicated in B cell activation; however, its involvement in the cytokine production of LPS-stimulated B cells remains less well characterized. Here, we show that the transient receptor potential melastatin 5 channel (TRPM5), which is one of the CAMs, negatively modulates calcium signaling, thereby regulating LPS-induced proliferative and inflammatory responses by B cells. LPS-stimulated B cells of Trpm5-deficient mice exhibit an increased cytosolic calcium concentration, leading to enhanced proliferation and the production of the inflammatory cytokines interleukin-6 and CXCL10. Furthermore, Trpm5-deficient mice show an exacerbation of endotoxic shock with high mortality. Our findings demonstrate the importance of TRPM5-dependent regulatory mechanisms in LPS-induced calcium signaling of splenic B cells.
AB - B cells produce high amounts of cytokines and immunoglobulins in response to lipopolysaccharide (LPS) stimulation. Calcium signaling cascades are critically involved in cytokine production of T cells, and the cytosolic calcium concentration is regulated by calcium-activated monovalent cation channels (CAMs). Calcium signaling is also implicated in B cell activation; however, its involvement in the cytokine production of LPS-stimulated B cells remains less well characterized. Here, we show that the transient receptor potential melastatin 5 channel (TRPM5), which is one of the CAMs, negatively modulates calcium signaling, thereby regulating LPS-induced proliferative and inflammatory responses by B cells. LPS-stimulated B cells of Trpm5-deficient mice exhibit an increased cytosolic calcium concentration, leading to enhanced proliferation and the production of the inflammatory cytokines interleukin-6 and CXCL10. Furthermore, Trpm5-deficient mice show an exacerbation of endotoxic shock with high mortality. Our findings demonstrate the importance of TRPM5-dependent regulatory mechanisms in LPS-induced calcium signaling of splenic B cells.
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U2 - 10.1016/j.celrep.2020.107755
DO - 10.1016/j.celrep.2020.107755
M3 - Article
C2 - 32521253
AN - SCOPUS:85086045179
SN - 2211-1247
VL - 31
JO - Cell Reports
JF - Cell Reports
IS - 10
M1 - 107755
ER -