Cockroach Allergen per a 7 Down-Regulates Expression of Toll-Like Receptor 9 and IL-12 Release from P815 Cells Through PI3K and MAPK Signaling Pathways

Abstract

Background: As a major source of indoor allergens, cockroach causes perennial rhinitis and asthma. Recently, cockroach feces were reported to contain TLR2 agonist, which could directly activate neutrophils to release cytokines. CpG oligodeoxynucleotide (ODN), a Toll-like receptor (TLR)9 activator was also found to induce proinflammatory cytokine release from mast cells. However, influence of specific cockroach allergen on Th1 cytokine release and expression of TLR9 in mast cells remains uninvestigated. Methods: To investigate effects of Per a 7 on TLR expression and cytokine release from mast cells and their cell signaling mechanisms, P815 cells were challenged by recombinant Per a 7 (rPer a 7), and expression of TLR9 mRNA and protein was assessed mainly by real time PCR and flow cytometry analysis. Detection of phosphorylation of cell signaling components was performed with Western blotting technique. Results: The results showed that rPer a 7 induced up to 72 and 46% down-regulation of expression of TLR9 mRNA and protein, respectively following 16 h incubation period. It induced also approximately 41.1% reduction of IL-12 release. When PD98059, U0126 and LY294002 were pre-incubated with the cells for 30 min they diminished rPer a 7 induced reduction of TLR9 expression and IL-12 release, indicating these events are via activation of ERK and PI3K/Akt signaling pathways. Conclusion: Reduction of IL-12 production and expression of TLR9 in P815 mastocytoma cells by Per a 7 suggests that this major cockroach allergen might contribute to the development of cockroach allergy.

Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells

“…wnt ligand WNT5A. p38 phosphorylation and p65/NFκB phosphorylation were also investigated as mediators of TLR signaling (Brown et al, 2011;DelaRosa and Lombardo, 2010;Yang et al, 2012). We found that p38 and p65 phosphorylation occurred after 30 min treatment with rhSAA1 in 3 different hMSC donors.…”

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

“…TLR3, 7, 8 and 9 are intracellular TLRs and their signaling cascade is depicted in figure 1 [19,23,41,42]. Viral infections, especially with rhinovirus, account for the most common causes of asthma exacerbation in children and cause more severe forms of wheezing episodes in allergic subjects [83].…”

“…This shows that not all infections and not all farming environments are protective. Interestingly, many triggers of asthma, such as environmental allergens and air pollutants, act in part via modulation in PRR expression and function [17,18,19,20]. Furthermore, the generation of reactive oxygen species is increased in asthma and AR, with oxidative stress being one factor that causes exacerbation of disease.…”

Cockroach allergen exposure and risk of asthma

“…They are generally complex heteropolymers, in contrast to the storage homopolymers that made up glycogen and amylose. More recently, intravenous and subcutaneous immunoglobulin preparations contain carbohydrate-specific IgG antibodies to microbial antigens, tumor-associated carbohydrate antigens, and host glycans (51), implicating the importance of these modifying macromolecules in human health and disease. Furthermore, polysaccharides, widely concerned as bioactive macromolecules in recent centuries, have been proved to benefit the intestinal health.…”