[BK21 Plus Seminar]
   
     
  ▶Subject: A novel mechanism of aspirin action on skin wound healing
         
  
  ▶Speaker: Takehiko Yokomizo, M.D., PH.D.

                     (Department of Biochemistry, Juntendo University School of Medicine)
           
  
  ▶Date: 4:00PM/Aug/6(Wed)/2014
          
    
  ▶Place: Auditorium(1F), Postech Biotech Center
          
  
         *Abctract
       Aspirin, the most famous non steroidal anti-inflammatory drug (NSAID), is widely used to kill pain and fever by inhibiting cyclooxygenases to produce prostaglandins (PGs). Aspirin is also famous for its serious side effects including mucosal damage of gastrointestinal tracts and delay in skin wound healing. Although reduced production of prostaglandins by aspirin is generally accepted as a common mechanism for these side effects, several reports using genetically engineered mice that lack PG production and PG receptors failed to prove the mechanism. We found that aspirin-dependent reduction of 12-hydroxyheptadecatrienoic acid (12-HHT), an endogenous ligand for leukotriene B4 receptor type 2 (BLT2), is responsible for the delay in skin wound healing. Aspirin delayed the wound closure after skin punching in mice, which was completely abolished in BLT2-deficient mice. Furthermore, mice deficient in BLT2 or thromboxane A2 synthase, a responsible enzyme for 12-HHT production, exhibited delayed wound healing. 12-HHT is produced during blood coagulation and activates BLT2 expressed in keratinocytes to release tumor necrosis factor ? and metalloproteinases to induce keratinocyte migration. A synthetic BLT2 agonist accelerated wound closure in vitro and in C57BL/6J and db/db mice. Our results clarify the novel mechanism of aspirin actions, and BLT2 agonists are possible therapeutic drugs for wounds especially for diabetic ulcer.
understanding the mechanisms of host-virus interactions are important biomedical goals. We have found that SK promotes the replication of influenza virus, whereas S1P-degrading enzyme S1P lyase inhibits influenza viral propagation and virus-induced cytopathic effects. While SK regulates influenza virus-induced intracellular signaling pathways, S1P lyase elevates type I IFN-induced antiviral signaling to inhibit virus replication. Thus, S1P-metabolizing enzymes are new therapeutic targets for the treatment of diseases caused by influenza virus infection.

  ▶Inquiry: Prof. Ryu, Sung Ho(279-2292)
         
   
   * This seminar will be given in English