Yan-Hou-Qing formula attenuates ammonia-induced acute pharyngitis in rats via inhibition of NF-κB and COX-2.

BACKGROUND: Yan Hou Qing (YHQ) is a Chinese medicinal formula designed to alleviate sore throat symptoms, but underlying mechanism of YHQ treatment for pharyngitis is poorly defined up to now. METHODS: In this study, the modulation of YHQ on pharyngitis is investigated in ammonia-induced acute pharyngitis rat models. After treatment with YHQ or dexamethasone respectively for five consecutive days, all rats were sacrificed for biomolecular and histopathologic study. Protein expressions of MAPKs, NF-κB, COX-2 and 5-LOX in pharyngitis tissue were evaluated by western blot analysis and the levels of TNF-α, IL-6, prostaglandin (PG) E2, leukotrienes (LT)-B4 and LT-D4 in pharyngeal tissue were measured via ELISA assay. Evans blue (EB) dye exudation test was performed parallelly to assess the integrity of pharyngeal tissue. RESULTS: Compared with normal control group, EB dye exudation, and inflammatory cytokines in the model group were significantly increased, and the pharynx tissue was obviously infiltrated by inflammatory cells. YHQ treatment improved the inflammatory infiltrate in pharyngeal tissue, and reduced EB dye exudation in AP rat models. The up-regulated TNF-α and IL-6 in pharyngeal tissue of AP were significantly reduced by YHQ through inhibition of phosphorylation of p38, Erk and NF-κB. YHQ treatment also reversed the increased level of PGE2 through down-regulation of COX-2. CONCLUSIONS: YHQ formula attenuated the pharyngitis related symptoms via suppression of COX-2 and phosphorylation of p38, Erk and NF-κB (p65).

Vasoactive intestinal peptide alleviates food allergy via restoring regulatory B cell functions.

The immune regulatory cell dysfunction is associated with many immune diseases including food allergy (FA). This study aims to investigate the role of vasoactive intestinal peptide (VIP) in the maintenance of regulatory B cell (Br cell)'s immune suppressive functions by stabilizing thrombospondin (TSP1) expression. In this study, blood samples were collected from patients with food allergy (FA) and healthy control (HC) subjects. Br cells were isolated from the samples through flow cytometry cell sorting and analyzed by immunological approaches to determine the immune regulatory capacity. We found that the immune suppressive functions of Br cells were impaired in FA patients. The serum VIP levels were associated with the production of immune suppressive function-related mediators (interleukin-10, IL-10) of Br cells in FA patients. VIP counteracted IL-10 mRNA decay in Br cells by up regulating the TSP1 expression. TSP1 inhibited tristetraprolin (TTP) to prevent IL-10 mRNA decay in Br cells. Administration of VIP inhibited FA response through restoration of immune suppressive functions in Br cells. In conclusion, administration of VIP can alleviate FA response through up regulating expression of TSP1 to stabilize IL-10 expression in FA Br cells and recover the immune regulatory functions. The results have translational potential for the treatment of FA and other disorders associated with immune regulatory dysfunction of Br cells.

Mal-deficiency impairs the tolerogenicity of dendritic cell of patients with allergic rhinitis.

The tolerogenic dendritic cell dysfunction is associated with the pathogenesis of immune diseases. Microbial stimulus is required in the maintenance of immune functions. This study aims to elucidate the role of Mal signal in the maintenance of DEC205+ DC (decDC) immune tolerogenic function. In this study, peripheral DCs were collected from allergic rhinitis (AR) patients and healthy control (HC) subjects to assess the functional status of decDCs. An AR murine model was developed to test the role of Mal signals in the maintenance of decDCs' functions. We observed that AR decDCs (decDCs obtained from AR patients) were incompetent in the induction of type 1 regulatory T cells (Tr1 cells). AR decDCs expressed less IL-10 than that in HC decDCs. IL-10 mRNA decayed spontaneously in AR decDCs. Tat-activating regulatory DNA-binding protein-43 (TDP43) protected IL-10 mRNA from decay. AR decDCs expressed lower levels of Mal than that in HC decDCs. Mal depletion resulted in IL-10 mRNA decay in HC decDCs. Reconstitution of Mal in AR decDCs restored the capacity of inducing Tr1 cells and attenuated experimental AR in mice. In conclusion, Mal plays a critical role in the maintenance of decDC's immune tolerogenic function. The absence or insufficient Mal signal impairs decDC's tolerogenic property. Reconstitution of Mal in AR decDCs can restore the immune tolerogenic capacity, which may have translational potential in the treatment of AR and other allergic diseases.

Deep Illumina sequencing reveals differential expression of long non-coding RNAs in hyperoxia induced bronchopulmonary dysplasia in a rat model.

BACKGROUND: Bronchopulmonary dysplasia (BPD) in premature infants is a predominantly secondary occurrence to intrauterine inflammation/infection and postpartum mechanical ventilation; The purpose of this study is to explore the biological roles of lincRNA in the pathogenesis of BPD. METHODS: Newborn rats were randomly assigned to hyperoxia (85% O2) or the control group: the normoxia group (21% O2). Lung tissues were collected on days 1-14. The BPD animal model was validated using HE staining, Masson staining, and real-time RT-PCR. Deep Illumina sequencing was used to reveal the differential expression of long non-coding RNAs in hyperoxia bronchopulmonary dysplasia rat models. KEGG and GO functions were predicted. Nine possible BPD-related target lincRNAs were verified by RTq-PCR. RESULTS: The histopathologic changes in lung tissues manifested as hyperaemia, edema, hemorrhage, and inflammation cell infiltration after continuous exposure to hyperoxia for 3 days, and became aggravated after 7 days of hyperoxic exposure. The above lung tissue inflammatory manifestations were alleviated and taken over by pulmonary interstitia hyperplasia and fibrocyte proliferation after 14 days of hyperoxic exposure. The expressions of lincRNA differed between the hyperoxia bronchopulmonary dysplasia model group and the normoxia group. 1175 different lincRNAs were detected in the hyperoxia group and the normoxia group, of which 544 were up-regulated and 631 were down-regulated. 673 moleculars related to GO functions were enriched, including cell location and biological process. Pathway enrichment analysis showed that lincRNA was involved in 257 KEGG pathways. 9 lincRNA were validated in the sample, and the difference was statistically significant. CONCLUSION: LincRNAs were identified differently between the BPD model and the normoxia group. Many target genes were involved in the developmental process, including cell component biogenesis, biological regulation, transcription regulator, and translation regulator. The BPD might be caused by the activation of the pathways of the EMC-receptor interaction, cytokine-cytokine receptor interaction, cell cycle, and cell adhesion molecules. The present study provides new insight into the pathogenesis mechanism of BPD.