Green Alga Ulva spp. Hydrolysates and Their Peptide Fractions Regulate Cytokine Production in Splenic Macrophages and Lymphocytes Involving the TLR4-NFkB/MAPK Pathways
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AuthorCian, Raúl E.; Hernández Chirlaque, Cristina; Gámez-Belmonte, Reyes; Drago, Silvina R.; Sánchez de Medina, Fermín; Martínez-Augustin, Olga
Bioactive peptidesGreen seaweedsInterleukin 10TLR2TLR4NFkB
Cian, R.E[et al.]. Green Alga Ulva spp. Hydrolysates and Their Peptide Fractions Regulate Cytokine Production in Splenic Macrophages and Lymphocytes Involving the TLR4-NFkB/MAPK Pathways. Mar. Drugs 2018, 16, 235; doi:10.3390/md16070235.
SponsorshipThis work was supported by funds from the Ministry of Economy and Competitivity, partly with Fondo Europeo de Desarrollo Regional FEDER funds [SAF2017-88457-R, AGL2017-85270-R, BFU2014-57736-P, AGL2014-58883-R] and by Junta de Andalucía [CTS235, CTS164]. C.H.-C. and R.G.-B. were supported by the University of Granada (Contrato Puente Program—Plan Propio) and the Ministry of Education [Spain], respectively. CIBERehd is funded by Instituto de Salud Carlos III.
Hydrolysates of food protein sources have immunomodulatory effects, which are of interest for use as functional foods. In this study, we have characterized the immune regulatory effect on rat splenocytes, macrophages and T lymphocytes of Ulva spp. hydrolysates and their peptide fractions with or without in vitro gastrointestinal digestion and/or ultrafiltration. IL-10 was induced in almost all conditions and cell types obtained from wild type animals. The induction was in general increased by ultrafiltration and in vitro gastrointestinal digestion. TNF was also induced in basal conditions. In turn, TNF and IFN- production was attenuated by the hydrolysate products in lipopolysaccharide or concanavalin A immune stimulated cells. Inhibitors for the activation of NF B, MAPK p38 and JNK inhibited IL-10 induction in rat splenocytes. The response was dramatically attenuated in TLR4-/- cells, and only modestly in TLR2-/- cells. Food peptides from Ulva spp. genus exert anti-inflammatory effects in immune cells mediated by TLR4 and NF B. Similarity with the immunomodulatory profile of protein hydrolysates from other sources suggests a common mechanism.