Role of transient receptor potential vanilloid 2 in LPS-induced cytokine production in macrophages

Kenji Yamashiro, Tetsuo Sasano, Katsuyoshi Tojo, Iyuki Namekata, Junko Kurokawa, Naoki Sawada, Takayoshi Suganami, Yasutomi Kamei, Hikaru Tanaka, Naoko Tajima, Kazunori Utsunomiya, Yoshihiro Ogawa, Tetsushi Furukawa

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


There is considerable evidence indicating that intracellular Ca2+ participates as a second messenger in TLR4-dependent signaling. However, how intracellular free Ca2+ concentrations ([Ca2+]i) is increased in response to LPS and how they affect cytokine production are poorly understood. Here we examined the role of transient receptor potential (TRP), a major Ca2+ permeation pathway in non-excitable cells, in the LPS-induced cytokine production in macrophages. Pharmacologic experiments suggested that TRPV family members, but neither TRPC nor TRPM family members, are involved in the LPS-induced TNFα and IL-6 production in RAW264 macrophages. RT-PCR and immunoblot analyses showed that TRPV2 is the sole member of TRPV family expressed in macrophages. ShRNA against TRPV2 inhibited the LPS-induced TNFα and IL-6 production as well as IκBα degradation. Experiments using BAPTA/AM and EGTA, and Ca2+ imaging suggested that the LPS-induced increase in [Ca2+]i involves both the TRPV2-mediated intracellular and extracellular Ca2+ mobilizations. BAPTA/AM abolished LPS-induced TNFα and IL-6 production, while EGTA only partially suppressed LPS-induced IL-6 production, but not TNFα production. These data indicate that TRPV2 is involved in the LPS-induced Ca2+ mobilization from intracellular Ca2+ store and extracellular Ca2+. In addition to Ca2+ mobilization through the IP3-receptor, TRPV2-mediated intracellular Ca2+ mobilization is involved in NFκB-dependent TNFα and IL-6 expression, while extracellular Ca2+ entry is involved in NFκB-independent IL-6 production.

Original languageEnglish (US)
Pages (from-to)284-289
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Jul 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


  • Calcium
  • Cytokine
  • LPS
  • Macrophage
  • Transient receptor potential vanilloid 2


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