Effect of mite allergenic components on innate immune response: Synergy of protease (Group 1 & 3) and non-protease (Group 2 & 7) allergens.

The major mite allergenic components of protease allergens (group 1,3) and non-protease allergens (group 2,7) derived from Dermatophagoides peronyssinus (Dp) and D. farinae (Df) are reported to be capable of sensitizing 80-90% of mite-allergic patients. Although protease and non-protease allergens have been demonstrated to trigger innate and adaptive immune responses through epithelium activation, the simultaneous or sequential effects of both groups of allergens has not been reported. Since all allergens are present in the mite crude extracts, it is important to determine whether these allergens can synergistically trigger the immune responses to cause airway inflammation. A total of 60 house dust mite (HDM)-allergic asthmatic patients were recruited to analyze their serum-specific IgE response to both groups of allergens. Recombinant protease allergen (Der p1 and Der p3) and non-protease allergens (Der p2 and Der p7) were used to activate the human airway epithelium cell (Beas-2B). The cells were analyzed for mRNA expression of IL-6/IL-8 and the culture supernatants were analyzed for neutrophil chemotactic activity (NCA). The results showed 48/60 (80%) HDM-allergic patients were sensitized to all allergenic components of Der p1, Der p2, Der f1, and Der f2. Most of the allergic patients were sensitized to both groups of allergens simultaneously. The associations of Der p1 with Der p2 were 83.3% (50/60) and Der f1 with Der f2 were 80% (48/60). When Beas-2B cells were cultured with Der p2 in conjunction with Der p1 and Der p3, the results showed that there was increased expression of IL-6/IL-8 in comparison with culture with allergen alone. There was only a trivial effect on IL-6/IL-8 expression when Der p2 was co-cultured with Der p7. Similar findings were obtained in the NCA measurement. When Beas-2B was cultured with Der p2 in conjunction with Der p1 and Der p3, there was increased NCA in comparison with culture with allergen alone. There were also trivial effects when Der p2 was co-cultured with Der p7. The allergens (Der p2 and Der p3)-induced IL-6/IL-8 expression and NCA released from Beas-2B could be downregulated by dexamethasone and transcription factor inhibitor SP600125. The allergenic components derived from Dp and Df can sensitize allergic patients simultaneously and activate epithelium through protease allergens (group 1, 3) and non-protease allergen (group 2) synergistically.

Alpinia oxyphylla Miq. fruit extract activates IGFR-PI3K/Akt signaling to induce Schwann cell proliferation and sciatic nerve regeneration.

BACKGROUND: It is known that the medicinal herb Alpinia oxyphylla Miq. is widely used as a remedy for diarrhea as well as the symptoms accompanying hypertension and cerebrovascular disorders. Moreover, it has also been reported that Alpinia oxyphylla Miq. has beneficial effects on anti-senescence and neuro-protection. This study focuses on the molecular mechanisms by which the Alpinia oxyphylla Miq. fruits promote neuron regeneration. METHODS: A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with various doses of Alpinia oxyphylla Miq. fruits to assess their regenerative effect on damaged nerves. Further, we investigated the role of Alpinia oxyphylla Miq. fruits in RSC96 Schwann cell proliferation. RESULTS: Our current results showed that treatment with the extract of Alpinia oxyphylla Miq. fruits triggers the phosphorylated insulin-like growth factor-1 receptor- phosphatidylinositol 3-kinase/serine-threonine kinase pathway, and up-regulated the proliferating cell nuclear antigen in a dose-dependent manner. Cell cycle analysis on RSC96 Schwann cells showed that, after exposure to Alpinia oxyphylla Miq. fruit extract, the transition from the first gap phase to the synthesis phase occurs in 12-18 h. The expression of the cell cycle regulatory proteins cyclin D1, cyclin E and cyclin A increased in a dose-dependent manner. Transfection with a small interfering RNA blocked the expression of phosphatidylinositol 3-kinase and induced down-regulation both on the mRNA and protein levels, which resulted in a reduction of the expression of the survival factor B-cell lymphoma 2. CONCLUSION: We provide positive results that demonstrate that Alpinia oxyphylla Miq. fruits facilitate the survival and proliferation of RSC96 cells via insulin-like growth factor-1 signaling.

Alpinia oxyphylla Miquel fruit extract activates MAPK-mediated signaling of PAs and MMP2/9 to induce Schwann cell migration and nerve regeneration.

OBJECTIVES: This study investigates the molecular mechanisms by which Alpiniae oxyphyllae fructus (AOF) promotes neuron regeneration. METHODS: A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of AOF extract (0-200 mg/ml). We investigated the role of MAPK (ERK1/2, JNK and p38) pathways for AOF-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in RSC96 Schwann cells. RESULTS: The results showed that AOF increased the expressions of uPA, tPA, MMP-9, and MAPKs in vivo. In vitro, our results show that treatment with AOF extract induces ERK1/2, JNK, and p38 phosphorylation to activate the downstream PAs and MMPs signaling expression. AOF-stimulated ERK1/2, JNK, and p38 phosphorylation attenuated by individual pretreatment with siRNAs or inhibitors (U0126, SP600125 and SB203580), resulting in migration and uPA-related signal pathway inhibition. CONCLUSIONS: Taken together our data suggests the MAPKs (ERK1/2, JNK and p38), PAs (uPA, tPA), MMP (MMP2, MMP9) regenerative and migration signaling pathway of Schwann cells regulated by AOF extract might play a major role in Schwann cell migration and damaged peripheral nerve regeneration.