Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

Abstract

This study investigated the immunomodulatory effects of ferulic acid (FA) on antigen-presenting dendritic cells (DCs) in vitro and its antiallergic effects against ovalbumin- (OVA-) induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation induced a high level of interleukin- (IL-) 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF-) α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4), MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE) and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13), and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN-) γ production in bronchoalveolar lavage fluid (BALF) and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model.

IL-10-Producing B Cells Regulate T Helper Cell Immune Responses during 1,3-β-Glucan-Induced Lung Inflammation

“…Our study demonstrated that insufficient B10 amplified the Th1 response, according to the increased number of Th1 cells, elevated levels of Th1 cytokine IFN-γ, and the continued high level of Th1 typical transcription factor T-bet. And this outcome was in accord with other studies (25, 44). On the other hand, T-bet is reported to be expressed in many cells of the adaptive and innate immune system, such as natural killer cells and dendritic cells, which might contribute to its continued high level at late time points.…”

Leonurus sibiricus root extracts decrease airway remodeling markers expression in fibroblasts

“…In turn, p-coumaric acid has been shown to decrease the production of IL-8 in cigarette smoke extract (CSE)stimulated A549 cells [65], and ferulic acid treatment was shown to suppress one of the main features of airway remodeling, indicated by reduction of mucus production [66], and to present anti-viral properties against RSV and influenza [67][68][69]. Therefore, it is possible that the cumulative action these substances may enable complementary remodeling treatment.…”

Ferulic acid promoting apoptosis in human osteosarcoma cell lines

“…FA could get the antioxidant activity in human dermal fibroblasts via increasing quantities of heat shock protein-70 and heme oxygenase-1 and decreasing lipid oxidation and hydrogen peroxide-induced protein 10. FA exhibits anti-inflammatory activity by modulating of dendritic cells functions to restore Th1/Th2 imbalance in the asthmatic mouse model 3. FA may modulate the status of lipid per-oxidation and antioxidants to contribute to anti-proliferative activity during the 7,12-dimethylbenz[a] anthracene-induced skin carcinogenesis 8.…”

“…FA (4-hydroxy-3-methoxycinnamic acid) is extracted from some natural plants, such as Asafoetida giantfennel, Angelica sinensis, Cimicifuga racemosa, Glycyrrhiza uralensis , and Ligusticum chuanxiong , which have been employed as the traditional Chinese herbs to treat multiple diseases for several thousand years 3-5. Recently, numerous literatures have demonstrated the antitumor activities and protective effects of FA on thyroid cancer, prostate cancer, skin carcinogenesis, lung cancer, etc 6-9.…”