PMID- 19232436 OWN - NLM STAT- MEDLINE DCOM- 20100125 LR - 20220408 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 47 IP - 1 DP - 2009 Nov TI - Proinflammatory and immunoregulatory mechanisms in periapical lesions. PG - 101-13 LID - 10.1016/j.molimm.2009.01.011 [doi] AB - Proinflammatory and immunoregulatory cytokines are important for the pathogenesis of periapical lesions. However, little is known about how their functions are balanced and controlled at different phases of lesion development. The aim of this study was to examine the relationship between the production of Th1, Th2, Th17 and T regulatory cell (T reg) cytokines by human periapical lesion mononuclear cells (PL-MNC) in culture and their correlation with cellular composition and clinical presentation of the lesions. We show that symptomatic lesions are characterized by the infiltration of neutrophils, high production of IL-17, positive correlation between IL-17 and IFN-gamma, but not between IL-17 and IL-23 production. Most IL-17(+) cells coexpressed IFN-gamma. Asymptomatic lesions were phenotypically heterogeneous. The lesions with the predominance of T cells over B cells/plasma cells expressed higher levels of IFN-gamma which correlated with higher production of IL-12 and the frequency of macrophages. In contrast, in most B-type lesions higher levels of IL-5 and TGF-beta were observed, as well as positive correlation between the production of TGF-beta and IL-10. The addition of Th cytokines in PL-MNC cultures confirmed that Th1, Th2 and Th17 cytokines are mutually antagonistic, except that IL-17, unexpectedly, augmented the production of IFN-gamma. IL-10 and TGF-beta inhibited the production of both Th1 and Th17 cytokines. Dendritic cells (DCs) from periapical lesions, composed of immature (CD83(-)), and mature (CD83(+)) myeloid type DCs and plasmacytoid (BDCA2(+)) DCs produced higher levels of IL-12 and IL-23 but lower levels of IL-10 and TNF-alpha than monocyte (Mo) -derived DCs. IL-23 stimulated the production of IL-17 by PL-MNC, whereas the secretion of IFN-gamma was enhanced by both IL-12 and IL-23. Cumulatively, these results suggest that: (1) Th1 immune response is most probably important for all stages of periapical lesion development; (2) Th2 and immunoregulatory cytokines are more significant for advanced types of lesions with the predominance of B cells/plasma cells; (3) Th17 immune response seems to play a dominant role in exacerbating inflammation. FAU - Colic, Miodrag AU - Colic M AD - Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11002 Belgrade, Serbia. vmaimi@eunet.rs FAU - Gazivoda, Dragan AU - Gazivoda D FAU - Vucevic, Dragana AU - Vucevic D FAU - Vasilijic, Sasa AU - Vasilijic S FAU - Rudolf, Rebeka AU - Rudolf R FAU - Lukic, Aleksandra AU - Lukic A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090215 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Cytokines) RN - 0 (Interleukins) SB - IM MH - B-Lymphocytes MH - Cells, Cultured MH - Cytokines/biosynthesis MH - Humans MH - Inflammation/immunology MH - Interleukins/biosynthesis MH - Neutrophil Infiltration MH - Periapical Diseases/*immunology/*pathology MH - Plasma Cells MH - T-Lymphocytes, Helper-Inducer/immunology MH - T-Lymphocytes, Regulatory/immunology EDAT- 2009/02/24 09:00 MHDA- 2010/01/26 06:00 CRDT- 2009/02/24 09:00 PHST- 2008/10/09 00:00 [received] PHST- 2008/12/24 00:00 [revised] PHST- 2009/01/08 00:00 [accepted] PHST- 2009/02/24 09:00 [entrez] PHST- 2009/02/24 09:00 [pubmed] PHST- 2010/01/26 06:00 [medline] AID - S0161-5890(09)00034-0 [pii] AID - 10.1016/j.molimm.2009.01.011 [doi] PST - ppublish SO - Mol Immunol. 2009 Nov;47(1):101-13. doi: 10.1016/j.molimm.2009.01.011. Epub 2009 Feb 15.