Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • Several MAP kinases are involved in

    2023-01-05

    Several MAP kinases are involved in the signal transduction pathways that lead to the upregulations of inflammatory mediators. Moreover, transcriptional activations of STATs are regulated by MAP kinases, as evidenced by reports that p38 MAPK is necessary for the S727 phosphorylation of STATs (Kovarik et al., 1999, Turkson et al., 1999). Interestingly, FSB reversed LPS-induced p38 MAPK phosphorylation only, which may have inhibited NF-κB translocation and its transcriptional activity. Separately, we examined the effects of FSB on the phosphorylations of STAT3 and AKT (upstream regulators of the transcriptional activities of AP-1 and NF-κB) and found that FSB inhibited the LPS-induced phosphorylations of STAT3 and AKT. Together, FSB suppressed LPS-induced Fusaric Acid at multiple levels, by inhibiting AKT/NF-κB and MAPKs/AP-1 pathways. LPS is the most frequent cause of sepsis, and thus, LPS-induced murine sepsis is widely utilized for the in vivo study of the anti-inflammatory effects of various agents. We found that FSB protected C57BL/6J mice from LPS-induced lethality and reduced the expressions of pro-inflammatory mediators in liver. In addition, the inhibitory effects of FSB on the iNOS, COX-2, AKT, p38 and STAT3 signaling pathways observed in vitro experiments were confirmed by our in vivo study. In summary, our findings show FSB inhibits LPS-induced inflammatory processes by inactivating STAT3, AKT, and p38 MAPK, subsequently suppressing the transcriptional activities of NF-κB and AP-1 in murine macrophages. More importantly, FSB protected C57BL/6J mice from LPS-induced septic lethality in vivo, which suggests FSB be considered a artificial selection potential therapeutics for the treatment of inflammatory and metabolic diseases.
    Acknowledgement This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant no. 2015R1D1A1A01058235) and the Korean Health Technology R&D Project of the Korean Health Industry Development Institute (KHIDI) funded by the Korean Ministry of Health & Welfare (Grant no. HI17C1296).