Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+) B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.

Cln3 blocks IME1 transcription and the Ime1-Ume6 interaction to cause the sporulation incompetence in a sake yeast, Kyokai no. 7.

Industrial yeasts, including a sake yeast Kyokai no. 7 (K7), are generally unable to sporulate. In K7 (Saccharomyces cerevisiae) cells, IME1 transcription was not induced under sporulation conditions, and K7 cells partially restored sporulation ability when transformed with a multicopy plasmid bearing IME1. However, the mechanisms of sporulation incompetence in industrial yeasts are poorly understood. We demonstrated that the deletion of the G1 cyclin CLN3, a key activator of the cell cycle, allows K7 cells to induce IME1 transcription and sporulate under sporulation conditions. In K7 cells, CLN3 mRNA and protein were not down-regulated despite sporulation conditions. Moreover, using a two-hybrid assay, we found that Ime1-Ume6 interaction was promoted in Cln3-deficient K7 cells. Thus, Cln3 is involved in the mechanism underlying sporulation incompetence by inhibiting IME1 transcription and the Ime1-Ume6 interaction. Based on these findings, we hypothesize that the absence of transmission of nutrient starvation signals to CLN3 leads to sporulation incompetence in K7 cells.

Alpha1-adrenergic receptor stimulation induces the expression of receptor activator of nuclear factor kappaB ligand gene via protein kinase C and extracellular signal-regulated kinase pathways in MC3T3-E1 osteoblast-like cells.

UNLABELLED: The receptor activator of nuclear factor kappaB ligand (RANKL) produced by bone marrow stromal/osteoblast cells is a crucial regulator of osteoclastgenesis and bone resorption. Osteoblastic cells have been demonstrated to express alpha(1)-adrenergic receptors. OBJECTIVE: The purpose of this study was to test the hypothesis that alpha(1)-adrenergic receptor stimulation induces the expression of RANKL gene via protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) pathways in osteoblastic cells. DESIGN: The steady-state mRNA levels of RANKL and activation of ERK in mouse MC3T3-E1 osteoblast-like cells were analyzed by semi-quantitative RT-PCR and Western blotting, respectively. RESULTS: In three alpha(1)-adrenergic receptor subtype mRNAs, alpha(1b)- and alpha(1d)-subtypes were expressed in MC3T3-E1 cells. The mRNA levels of RANKL were increased by phenylephrine (alpha(1)-agonist) in time- and dose-dependent manners. Prazosin (alpha(1)-antagonist) suppressed the phenylephrine-induced RANKL mRNA expression, but yohimbine (alpha(2)-antagonist) and propranolol (beta-antagonist) did not. Phorbol 12-myristate 13-acetate (PMA, PKC activator) increased RANKL mRNA expression and GF109203X (PKC inhibitor) suppressed the phenylephrine-induced RANKL mRNA expression. Both phenylephrine and PMA stimulated the phosphorylation of ERK, while both prazosin and GF109203X inhibited phenylephrine-induced ERK activation. Pretreatment with PD98059 (ERK kinase inhibitor) inhibited both the phosphorylation of ERK and the expression of RANKL gene induced by phenylephrine in MC3T3-E1 cells. CONCLUSION: These results show that alpha(1b)- and alpha(1d)-adrenergic receptor subtype genes are expressed and the expression of RANKL mRNA may be regulated by alpha(1)-adrenergic receptor stimulation in osteoblastic cells. The induction of RANKL mRNA by activating the alpha(1)-adrenergic receptor is probably mediated via PKC and ERK signalling pathways in osteoblastic cells.