Abstract OBJECTIVE: Gram-negative bacteria-induced multiple organ failure/dysfunction syndrome (MOF/MODS) is one of the leading causes of death through the world. The member of immunoglobulin family programmed death-1 (PD-1) is a negative immune regulator. This study investigated the protective effect of PD-1 as well as the underlying mechanism in LPS-induced endotoxemia. METHODS: Ten PD-1+/+ and ten PD-1 knockout (PD-1/) mice were injected peritoneally with LPS (10 mg/kg), and the survival was observed within 72 hrs after LPS injection. The other 40 PD-1+/+ and 40 PD-1/mice were injected peritoneally with LPS (5 mg/kg). Blood samples were collected before injection and 1.5, 3 and 6 hrs after LPS injection (n=10 each time point). Serum levels of various inflammatory mediators were measured using ELISA. RESULTS: The survival rate in PD-1/mice was noticeably lower than that in PD-1+/+ mice after 10 mg/kg LPS injection. Serum levels of inflammatory mediators TNF-α, IL-1β, IL-12 and IL-17 in PD-1/mice were higher than those in PD-1+/+ mice after 5 mg/kg LPS injection. CONCLUSIONS: PD-1 can protect mice from LPS-induced endotoxemia probably through its regulation on inflammatory mediator production.［Chin J Contemp Pediatr, 2010, 12 (10):812-815］
YANG Li-Fen,HE Fang,ZHANG Jian et al. Protection of PD-1 against LPS-induced endotoxemia and the underlying mechanism[J]. 中国当代儿科杂志, 2010, 12(10): 812-815.
YANG Li-Fen,HE Fang,ZHANG Jian et al. Protection of PD-1 against LPS-induced endotoxemia and the underlying mechanism[J]. CJCP, 2010, 12(10): 812-815.
［1］Annane D, Bellissant E, Cavaillon JM. Septic shock ［J］. Lancet, 2005, 365 (9453): 63-78.
［2］Karima R, Matsumoto S, Higashi H, Matsushima K. The molecular pathogenesis of endotoxic shock and organ failure ［J］. Mol Med Today, 1999, 5 (3): 123-132.
［3］Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity ［J］. Annu Rev Immunol, 2008, 26: 677-704.
［4］Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection ［J］. Nat Immunol, 2007, 8 (3): 239-245.
［5］Nishimura H, Honjo T. PD-1: an inhibitory immunoreceptor involved in peripheral tolerance ［J］. Trends Immunol, 2002, 22 (5): 265-268.
［6］Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor ［J］. Immunity, 1999, 11 (2): 141-151.
［7］Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice ［J］. Nat Med, 2003, 9 (12): 1477-1483.
［8］Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice ［J］. Science, 2001, 291(5502): 319-322.
［9］Zhao Q, Wang X, Nelin LD, Yao Y, Matta R, Manson ME, et al. MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock ［J］. J Exp Med, 2006, 203 (1): 131-140.
［11］Wynn J, Cornell TT, Wong HR, Shanley TP, Wheeler DS. The host response to sepsis and developmental impact ［J］. Pediatrics, 2010, 125 (5): 1031-1041.
［12］Peleg AY, Hooper DC. Hospital-acquired infections due to gram-negative bacteria ［J］. N Engl J Med, 2010, 362 (19): 1804-1813.
［13］Gioannini TL, Weiss JP. Regulation of interactions of Gram-negative bacterial endotoxins with mammalian cells ［J］. Immunol Res, 2007, 39 (1-3): 249-260.
［14］Janeway CA Jr, Medzhitov R. Innate immune recognition ［J］. Annu Rev Immunol, 2002, 20: 197-216.
［17］Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death ［J］. EMBO J, 1992, 11 (11): 3887-3895.
［18］Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance ［J］. Trends Immunol, 2006, 27 (4): 195-201.
［19］Prokunina L, Padyukov L, Bennet A, de FU, Wiman B, Prince J, et al. Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope ［J］. Arthritis Rheum, 2004, 50 (6): 1770-1773.
［20］Nielsen C, Hansen D, Husby S, Jacobsen BB, Lillevang ST. Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes ［J］. Tissue Antigens, 2003, 62 (6): 492-497.
［21］Kong EK, Prokunina-Olsson L, Wong WH, Lau CS, Chan TM. AlarconRiquelme M, et al. A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese ［J］. Arthritis Rheum, 2005, 52 (4): 1058-1062.
