The pathophysiology of periapical lesions (PLs) is under control of pro-inflammatory and anti-inflammatory (mainly immunoregulatory) cytokines. We have recently established mesenchymal stem cells (MSCs) from PLs and showed their suppressive effects on the production of proinflammatory cytokines from PLs inflammatory cells (ICs). In this work we studied the production of interleukin (IL)-10, IL-27 and transforming growth factor (TGF)-β, by PL-ICs in direct or indirect contacts with PL-MSCs. PL-ICs, which were isolated from four different asymptomatic PLs, predominantly composed of lymphocytes, followed by neutrophil granulocytes, macrophages and plasma cells. PLMSCs, expressing typical MSC markers, were co-cultivated with PL-ICs at 1:10 ratio, either in direct contact or in a transwell-system, for 24 hours. The levels of cytokines in cell-culture supernatants were tested by ELISA. The results showed that PL-MSCs up-regulated the production of all three immunoregulatory cytokines by PL-ICs. PL-MSCs stimulated the production of IL-10 and IL-27 via soluble factors, whereas the up-regulation of TGF-β required direct cell-to-cell contacts. In conclusion, our results showed for the first time the involvement of PL-MSCs in restriction of inflammation in PLs by up-regulation of immunoregulatory cytokines. Patofiziologija periapikalnih lezija (PLs) je pod kontrolom proinflamacijskih i antiinflamacijskih (uglavnom imunoregulacijskih) citokina. U našem ranijem radu uspostavili smo ćelijsku liniju mezenhimalnih matičnih ćelija (MSCs) iz PLs i pokazali njihov supresivni efekat na produkciju proinflamacijskih citokina od strane inflamacijskih ćelija iz periapekalnih lezija (PL-ICs). U ovom radu smo proučavali produkciju IL-10, IL-27 i transformišućeg faktora rasta (TGF)-β, od strane PL-ICs u direktnom ili indirektnom kontaktu sa PL-MSCs. Izolovane PL-ICs iz četiri različite asimptomatske PLs pretežno čine limfociti, zatim granulociti, makrofagi i plazma ćelije. PL-MSCs, za koje je pokazano da eksprimiraju tipične MSCs markere, kultivisane su sa PL-ICs u odnosu 1:10 u direktnoj ko-kulturi ili korišćenjem umetaka koji onemogućavaju direktan međućelijski kontakt u toku 24 časa. Nivo citokina u supernatantima ćelijskih kultura određivan je pomoću ELISA metode. Rezultati pokazuju da PL-MSCs povećavaju produkciju sva tri imunoregulatorna citokina od strane PL-ICs. PL-MSCs stimulišu produkciju IL-10 i IL-27 preko solubilnih faktora, dok je za povećanje TGF-β neophodan direktan ćelijski kontakt. U zaključku, naši rezultati pokazuju po prvi put da PL-MSCs imaju ulogu u ograničavanju inflamacije PLs povećanjem produkcije imunoregulacijskih citokina.