Cutting edge Seminar

 

 

Speaker: Takehiko Yokomizo  (Professor,   Department of Molecular and Cellular Biochemistry, Juntendo University School of Medicine)

Title: Biology of 12-hydroxyheptadecatrienoic acid, a novel COX-derived lipid mediator

 

 

 

Date&Time:  21 Jun. (Wed.) 2017, 12:00- 13:00
Venue: Conference Room(1F), IMEG

 

Abstract:

Non-steroidal anti-inflammatory drugs (NSAID) exert their effects by inhibiting the production of prostaglandins (PG) and thromboxanes (Tx). The reduced production of PG and Tx sometimes cause problematic side effects of NSAID. We identified another cyclooxygenase (COX) product 12-hydroxyheptadecatrienoic acid (12-HHT) as a bona fide ligand for BLT2 receptor (1), originally cloned as a low-affinity leukotriene B4 receptor (2). BLT2 is expressed in cells facing to the external environment such as keratinocytes, intestinal epithelial cells (3), and corneal cells, and involved in skin and corneal wound healing (4) and maintenance of epidermal barrier function (5). Some side effects of NSAID such as delayed wound healing in skin and cornea are caused by the reduction of 12-HHT. In this lecture, we will discuss on the strategy how we identified 12-HHT/BLT2 axis as a downstream molecules of COXs, and possible application of BLT2 activation in several human diseases (6).

 

References:

1. Okuno, T, Iizuka, Y, Okazaki, H, Yokomizo, T, Taguchi, R, Shimizu, T. 12(S)-Hydroxyheptadeca-5Z, 8E, 10E-trienoic acid is a natural ligand for leukotriene B4 receptor 2. J Exp Med 205, 759-766 (2008)
2. Yokomizo, T, Kato, K, Terawaki, K, Izumi, T, Shimizu, T. A second leukotriene B(4) receptor, BLT2. A new therapeutic target in inflammation and immunological disorders. J Exp Med 192, 421-432 (2000)
3. Iizuka, Y, Okuno, T, Saeki, K, Uozaki, H, Okada, S, Misaka, T, Sato, T, Toh, H, Fukayama, M, Takeda, N, Kita, Y, Shimizu, T, Nakamura, M, Yokomizo, T. Protective role of the leukotriene B4 receptor BLT2 in murine inflammatory colitis. FASEB J 24, 4678-4690 (2010)
4. Liu, M, Saeki, K, Matsunobu, T, Okuno, T, Koga, T, Sugimoto, Y, Yokoyama, C, Nakamizo, S, Kabashima, K, Narumiya, S, Shimizu, T, Yokomizo, T. 12-hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor. J Exp Med 211, 1063-1078 (2014)
5. Ishii, Y, Saeki, K, Liu, M, Sasaki, F, Koga, T, Kitajima, K, Meno, C, Okuno, T, Yokomizo, T. Leukotriene B4 receptor type 2 (BLT2) enhances skin barrier function by regulating tight junction proteins. FASEB J 30, 933-947 (2016)
6. Yokomizo, T. Two distinct leukotriene B4 receptors, BLT1 and BLT2. J Biochem 157, 65-71 (2015)