Dataset Information

Longistatin in tick saliva blocks advanced glycation end-product receptor activation.

ABSTRACT: Ticks are notorious hematophagous ectoparasites and vectors of many deadly pathogens. As an effective vector, ticks must break the strong barrier provided by the skin of their host during feeding, and their saliva contains a complex mixture of bioactive molecules that paralyze host defenses. The receptor for advanced glycation end products (RAGE) mediates immune cell activation at inflammatory sites and is constitutively and highly expressed in skin. Here, we demonstrate that longistatin secreted with saliva of the tick Haemaphysalis longicornis binds RAGE and modulates the host immune response. Similar to other RAGE ligands, longistatin specifically bound the RAGE V domain, and stimulated cultured HUVECs adhered to a longistatin-coated surface; this binding was dramatically inhibited by soluble RAGE or RAGE siRNA. Treatment of HUVECs with longistatin prior to stimulation substantially attenuated cellular oxidative stress and prevented NF-?B translocation, thereby reducing adhesion molecule and cytokine production. Recombinant longistatin inhibited RAGE-mediated migration of mouse peritoneal resident cells (mPRCs) and ameliorated inflammation in mouse footpad edema and pneumonia models. Importantly, tick bite upregulated RAGE ligands in skin, and endogenous longistatin attenuated RAGE-mediated inflammation during tick feeding. Our results suggest that longistatin is a RAGE antagonist that suppresses tick bite-associated inflammation, allowing successful blood-meal acquisition from hosts.

SUBMITTER: Anisuzzaman

PROVIDER: S-EPMC4191044 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Longistatin in tick saliva blocks advanced glycation end-product receptor activation.

Anisuzzaman Hatta Takeshi T Miyoshi Takeharu T Matsubayashi Makoto M Islam M Khyrul MK Alim M Abdul MA Anas M Abu MA Hasan M Mehedi MM Matsumoto Yasunobu Y Yamamoto Yasuhiko Y Yamamoto Hiroshi H Fujisaki Kozo K Tsuji Naotoshi N

The Journal of clinical investigation 20141001 10

Ticks are notorious hematophagous ectoparasites and vectors of many deadly pathogens. As an effective vector, ticks must break the strong barrier provided by the skin of their host during feeding, and their saliva contains a complex mixture of bioactive molecules that paralyze host defenses. The receptor for advanced glycation end products (RAGE) mediates immune cell activation at inflammatory sites and is constitutively and highly expressed in skin. Here, we demonstrate that longistatin secrete ...[more]

PMID: 25401185

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Project description:BackgroundAdvanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking.ObjectivesWe examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6 ± 2.9 y; 52% female; 37% black).MethodsCML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults: <0.8 g/kg/d (n = 1077), 0.8 to <1.2 g/kg/d (n = 922), and ≥1.2 g/kg/d (n = 440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression models adjusted for demographics, height, lifestyle behaviors, prevalent disease, cognitive function, inflammation, and other dietary factors.ResultsCML concentrations were higher in individuals with higher total protein intake (adjusted least squares mean ± SE: <0.8 g/kg/d, 829 ± 17 ng/ml; 0.8 to <1.2 g/kg/d, 860 ± 15 ng/ml; ≥1.2 g/kg/d, 919 ± 23 ng/ml; P for trend = 0.001), as were sRAGE concentrations (<0.8 g/kg/d, 1412 ± 34 pg/ml; 0.8 to <1.2 g/kg/d, 1479 ± 31 pg/ml; ≥1.2 g/kg/d, 1574 ± 47 pg/ml; P for trend < 0.0001). Every 0.1 g/kg/d increment in total protein intake was associated with a 13.3 ± 3.0 ng/ml increment in CML and a 22.1 ± 6.0 pg/ml increment in sRAGE (P < 0.0001 for both). Higher CML and sRAGE concentrations were also associated with higher intakes of both animal and vegetable protein (all P values ≤ 0.01). There were no significant associations with the CML/sRAGE ratio.ConclusionsHigher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.

Dataset Information

Longistatin in tick saliva blocks advanced glycation end-product receptor activation.

Publications

Longistatin in tick saliva blocks advanced glycation end-product receptor activation.

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