Propolis effects on pro-inflammatory cytokine production and Toll-like receptor 2 and 4 expression in stressed mice.
BACKGROUND
Propolis is a beehive product and its immunomodulatory action has been well documented; however, little is known concerning its activity on the immune system of stressed mice. This work investigated a possible role of propolis against the immunosuppressive effects induced by stress in mice, assessing the pro-inflammatory cytokine (IL-1beta and IL-6) production and Toll-like receptor (TLR-2 and TLR-4) expression by spleen cells.


METHODS
BALB/c mice were divided into 3 groups: G1 was considered control; G2 was submitted to restraint stress for 3 days, and G3 was treated with propolis and immediately submitted to stress. After sacrifice, spleens were removed and TLR-2 and TLR-4 gene expression was analyzed, as well as the pro-inflammatory cytokine production. Serum corticosterone levels were determined by radioimmunoassay as a stress indicator.


RESULTS
Stressed mice, treated or not with propolis, produced higher corticosterone levels, whereas IL-1beta and IL-6 production was inhibited. TLR-2 and TLR-4 expression was inhibited in stressed mice, while propolis exerted an immunorestorative role in TLR-4 expression. The immunosuppressive effects on IL-1beta and IL-6 production and on TLR expression by stressed mice might have occurred due to a higher corticosterone production during stress.


CONCLUSIONS
Propolis treatment did not antagonize the inhibitory effects on pro-inflammatory cytokine production, however it restored at least partially TLR2 mRNA expression and counteracted the inhibition on TLR-4 expression in stressed animals, contributing to the recognition of microorganisms during stressful conditions.
Pagliarone
Ana Carolina
AC
Department of Microbiology and Immunology, Biosciences Institute, UNESP, 18618-000 Botucatu, SP, Brazil.
Orsatti
Cláudio Lera
CL
Búfalo
Michelle Cristiane
MC
Missima
Fabiane
F
Bachiega
Tatiana Fernanda
TF
Júnior
João Pessoa Araújo
JP
Sforcin
José Maurício
JM
D000818:Animals; D001688:Biological Products / Q000627:therapeutic use; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D053583:Interleukin-1beta / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011429:Propolis / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D012149:Restraint, Physical; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D001688:Biological Products; D007155:Immunologic Factors; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D011429:Propolis; D003345:Corticosterone