Biomolecules & Therapeutics, 16, 351-355(2008) www.biomolther.org Immunosuppressive Effect of Prodigiosin on Murine Splenocyte and Macrophages Jung-Eun HUH 1 , Hyun-Jung KOO 1 , Kyung-Ho, KIM 1 , Joung-Han YIM 2 , Hong-Kum LEE 2 , Eun-Wha SOHN 3 , and Suhkneung PYO 1 1 Devision of Immunopharmacology, College of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea. 2 Polar BioCenter, Korea Polar Research Institute, KORDI, Incheon, 406-840, Republic of Korea 3 Department of Pharmacognosy and Material development, Kangwon National University, Samcheok city, Kangwon-do, 245-711, Republic of Korea (Received October 24, 2008; Revised November 19, 2008; Accepted November 21, 2008) Abstract - Prodigiosin was isolated from marine bacteria Hahella chejuensis which has been recently discov- ered from Marado, Cheju Island, Republic of Korea. Immunosuppressive properties have been reported for pro- digiosin members such as undecylprodigiosin, metacycloprodigiosin, prodigiosin, and its synthetic analogue PNU156804 (PNU). However, the effect of this agent on the function of macrophage and splenocyte has not been characterized in detail. In the present study, we examined the effects of prodigiosin for its ability to alter the function of murine macrophage and NK cell, and the proliferation of splenocytes. When thioglycollate-elicited macrophages pre-exposed to prodigiosin (1-50 ng/ml) were stimulated with LPS/IFN-γ, pretreatment with prodi- giosin resulted in the inhibition of tumoricidal activity of macrophage in a concentration-dependent manner. Tumoricidal activity of NK cell was also inhibited by prodigiosin. Moreover, we found that prodigiosin was able to cause a dose-dependent inhibition of murine lymphocyte responsiveness to Con A and LPS although T-mitoge- nic response was the more sensitive one. Taken together, the present results point out that prodigiosin has a suppressive effect on the mitogen-induced proliferation of murine lymphocytes and the function of macrophage and NK cell. Keywords : Hahella chejuensis, Prodigiosin, Immunosuppression, Macrophages, Splenocyte INTRODUCTION There has been increasing interest in the discovery and development of novel pharmaceuticals from marine microorganisms that have the same or better immuno- suppressants accompanied by less side effects. Recently, the only species of the genus, Hahella chejuensis, was isolated from the coastal marine sediment of the south- ernmost island in Korea and the complete genome sequence of H.chejuensis in its class was determined (Jeong et al., 2005). This bacterium produces abundant extracellular polysaccharides and prodigosin (Lee et al., 2001). Prodigiosins are a family of natural red pigments containing three pyrrole rings produced by S. marce- scens, Pseudomonas magnesiorubra, Vibrio psychro- erythrus and other bacteria. Some members of this family, including prodigiosin, have been suggested to have immunosuppressive activity, which suppress cyto- toxic T cells by inhibition of acidification of intracellular organelles without affecting B cell-mediated immune functions, different from that of the other well known immunosuppressors such as cyclosporine A, FK506 and rapamycin (Kataoka et al., 1995; Songia et al., 1997; Pandeya et al., 2003). However, the effect of prodigiosin on the function of macrophage, Natural killer (NK) cells and splenocyte is less well understood. Macrophages and NK cells in peripheral blood play important roles in the antigen-independent initial host defense system against infection with various microbes. NK cells are an important component of the innate immune system and mediate the cytolytic activities against tumor and virus-infected targets. In addition to the cytotoxic activity, there are increasing indications that NK cells can secrete a variety of cytokines and cytotoxic fac- *Corresponding author Tel: +82-31-290-7713 Fax: +82-31-292-8800 E-mail: snpyo@skku.edu ISSN: 1976-9148(print)/2005-4483(online) DOI: 10.4062/biomolther.2008.16.4.351