The destructive effects of ROS are highly connected to cytokine responses involved in repairing intestinal injury when the oxidative damage in the inflamed mucosa correlates with IBD intensity [
22]. The existence of specific polymorphism, dinucleotide repeat of the IL11.A1 allele, in IL-11 was significantly associated with UC have been seen in various studies [
23]. Making use of recombinant human IL-11 able to maintain remission phase in Crohn’s disease [
24]. Nevertheless, there are few different theories concerning the role that IL-11 plays to promote colitis into colorectal cancer while the alleviating function of IL-11 in colitis has been detected [
16]. The direct effects of IL-11 can differentiate CD4
+ T cells into Th2 cells which is a dominant subset of T effectors in UC [
25]. In other Th2-dominant inflammatory diseases, like asthma, the high level of IL-11 has been measured [
26]. A previous study reported the decreasing of
IL-11 gene expression in mild and severe UC patients, but did not assess IL-11 intestinal or serum protein levels [
21]. In contrast to this study, we detected an enhanced IL-11 protein expression in mild UC. Some investigations on mice showed that the protective and restorative roles of IL-11 elevated when the murine intestinal cells were exposed to radiation or chemical stresses. IL-11 was considered as a mucosal protective in addition to retraining the apoptosis of mature enterocytes [
27,
28]. Our data illustrated that
Fra-1 gene expression had a similar pattern with an expression of the IL-11 protein. Furthermore,
Fra-1 gene expression in our analysis positively correlated with IL-11 expression in the mild patient group. Fra-1 factor is an essential mediator to induce IL-11 through oncogenic Ras activation. The human pancreatic carcinoma cells decreased serum induce-IL-11 in response to Fra-1 blocking siRNA even after making use of Ras activator [
29].Both Fra-1 and IL-11 are relatively overexpressed in oxidative stress condition. Extracellular signal-regulated kinase2 (ERK2), which is stimulated by ROS components, induces Fra-1 in retinal, liver and CRC cell [
10,
13,
30]. Pro-inflammatory cytokines such as IL-18 and IL-6 are able to stimulate MAPK pathway leading to increasing epithelium-derived IL-11 in DSS mice model [
11,
31]. It has been elucidated that the targeting AP-1 factor through oligodeoxynucleotide (ODN) therapy reduces histological inflammation in DSS-induced experimental murine colitis [
12]. Oxidative stress, along with Fra-1 factor, can activate other transcription factors including NRF-2 and HIF-1 that up-regulate IL-11 transcription [
32]. Mothers against decapentaplegic homolog 3 (SMAD3) is affected by microenvironment in UC patients and is altered into pSmad3L/C form. Accordingly, SMAD3 and Runt-related transcription factor 2 (RUNX2) bind to the
IL-11 promoter in order to transcript
IL-11 gene [
33,
34]. These factors lead to the production of IL-11 protein in mild UC. However, IL-11 and
Fra-1 expression are decreased in severe UC mucosa remains unclear. Our observations suggest the possibility that consuming corticosteroid drug in severe UC patients may inhibit Fra-1 and IL-11 in the following. In fact the loss of AP-1 and NF-kB factors as a result of corticosteroids effects consequently inhibits IL-11 production [
35,
36]. On the other hand, transforming Growth Factor beta (TGF-β1) which is an essential co-factors with Fra-1 to induce IL-11, is significantly decreased in active form of UC patients [
37]. Otherwise, further investigations are needed to characterize molecular mechanisms responsible for IL-11 and
Fra-1 gene expression. In addition, specific cells that produce IL-11 in UC intestine should be clearly detected. In sum, we demonstrated that IL-11 protein expression is increased in the colonic biopsy of mild UC patients. Our data suggest that epithelial cells under oxidative stress trigger
Fra-1 and IL-11 expression in the following.