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Cell-penetrating peptide derived from human eosinophil cationic protein inhibits mite allergen Der p 2 induced inflammasome activation.

Yu SJ, Liao EC, Sheu ML, Chang DT, Tsai JJ - PLoS ONE (2015)

Bottom Line: The aim of this study was to investigate the immunomodulatory effect of CPPecp on inhibition of Der p 2 induced inflammasome activation.The immunomodulatory effect of CPPecp was through upregulation of IFN-α production but not induction of autophagy.These results suggested Der p 2 plays an important role in NLRP3 inflammasome activation and CPPecp has the potential to be a novel anti-inflammatory agent for allergic inflammation treatment in the future.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.

ABSTRACT
Newly discovered cell penetration peptides derived from human eosinophil cationic proteins (CPPecp) have the characteristic of cell internalization, but the effect of CPPecp on immunomodulation has not been clarified. House dust mite (HDM) major allergen, Der p 2, can induce proinflammatory cytokine production which contributes to airway inflammation and allergic asthma. However, the mechanism of Der p 2 on NLRP3 inflammasome activation remains unclear. The aim of this study was to investigate the immunomodulatory effect of CPPecp on inhibition of Der p 2 induced inflammasome activation. We showed that proinflammatory cytokines IL-1β, IL-6 and IL-8 were significantly upregulated in peripheral blood mononuclear cells (PBMCs) derived from HDM allergic patients after Der p 2 stimulation. Expression of NLRP3, ASC, Caspase-1, IL-1β and Caspase-1 activity was upregulated in THP-1 cells after Der p 2 stimulation. Proinflammatory cytokine production, NLRP3 inflammasome activation and caspase-1 activity were downregulated in THP-1 cells and CD14+ cells co-cultured with Der p 2 and CPPecp. The immunomodulatory effect of CPPecp was through upregulation of IFN-α production but not induction of autophagy. These results suggested Der p 2 plays an important role in NLRP3 inflammasome activation and CPPecp has the potential to be a novel anti-inflammatory agent for allergic inflammation treatment in the future.

No MeSH data available.


Related in: MedlinePlus

Der p 2 induces pro-inflammatory cytokine expression in HDM allergic patients.PBMCs derived from HDM allergic patients (n = 6) were stimulated with Der p 2 (1.5ug/ml) for six hours; LPS (500ng/ml) was used as control. After stimulation, the culture supernatant was collected and protein levels of IL-1β, IL-6 and IL-8 were measured by ELISA. Bars and error bars indicate mean and standard error of the mean (SEM), respectively. * p<0.05 compared to control group.
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pone.0121393.g001: Der p 2 induces pro-inflammatory cytokine expression in HDM allergic patients.PBMCs derived from HDM allergic patients (n = 6) were stimulated with Der p 2 (1.5ug/ml) for six hours; LPS (500ng/ml) was used as control. After stimulation, the culture supernatant was collected and protein levels of IL-1β, IL-6 and IL-8 were measured by ELISA. Bars and error bars indicate mean and standard error of the mean (SEM), respectively. * p<0.05 compared to control group.

Mentions: Allergen induced pro-inflammatory cytokine production is associated with allergic inflammation. We investigated the correlation between mite major allergen-Der p 2 and allergic inflammation by culturing PBMCs derived from six HDM allergic subjects cultured with Der p 2 (1.5ug/ml) or LPS (500ng/ml) for six hours. Culture supernatant was collected for cytokine measurement by ELISA. The results showed that IL-1β, IL-6 and IL-8 were significantly upregulated after Der p 2 stimulation (p<0.05; Fig. 1). Furthermore, we investigated the effect of Der p 2 is specific to HDM allergic patients, CD14+ cells derived from two non HDM allergic patients were cultured with Der p 2 (1.5ug/ml) or LPS (500ng/ml) for six hours. Secreted IL-1β, IL-6 and IL-8 in the culture supernatant were not increase after Der p 2 stumulation (S1 Fig.)


Cell-penetrating peptide derived from human eosinophil cationic protein inhibits mite allergen Der p 2 induced inflammasome activation.

Yu SJ, Liao EC, Sheu ML, Chang DT, Tsai JJ - PLoS ONE (2015)

Der p 2 induces pro-inflammatory cytokine expression in HDM allergic patients.PBMCs derived from HDM allergic patients (n = 6) were stimulated with Der p 2 (1.5ug/ml) for six hours; LPS (500ng/ml) was used as control. After stimulation, the culture supernatant was collected and protein levels of IL-1β, IL-6 and IL-8 were measured by ELISA. Bars and error bars indicate mean and standard error of the mean (SEM), respectively. * p<0.05 compared to control group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4373874&req=5

pone.0121393.g001: Der p 2 induces pro-inflammatory cytokine expression in HDM allergic patients.PBMCs derived from HDM allergic patients (n = 6) were stimulated with Der p 2 (1.5ug/ml) for six hours; LPS (500ng/ml) was used as control. After stimulation, the culture supernatant was collected and protein levels of IL-1β, IL-6 and IL-8 were measured by ELISA. Bars and error bars indicate mean and standard error of the mean (SEM), respectively. * p<0.05 compared to control group.
Mentions: Allergen induced pro-inflammatory cytokine production is associated with allergic inflammation. We investigated the correlation between mite major allergen-Der p 2 and allergic inflammation by culturing PBMCs derived from six HDM allergic subjects cultured with Der p 2 (1.5ug/ml) or LPS (500ng/ml) for six hours. Culture supernatant was collected for cytokine measurement by ELISA. The results showed that IL-1β, IL-6 and IL-8 were significantly upregulated after Der p 2 stimulation (p<0.05; Fig. 1). Furthermore, we investigated the effect of Der p 2 is specific to HDM allergic patients, CD14+ cells derived from two non HDM allergic patients were cultured with Der p 2 (1.5ug/ml) or LPS (500ng/ml) for six hours. Secreted IL-1β, IL-6 and IL-8 in the culture supernatant were not increase after Der p 2 stumulation (S1 Fig.)

Bottom Line: The aim of this study was to investigate the immunomodulatory effect of CPPecp on inhibition of Der p 2 induced inflammasome activation.The immunomodulatory effect of CPPecp was through upregulation of IFN-α production but not induction of autophagy.These results suggested Der p 2 plays an important role in NLRP3 inflammasome activation and CPPecp has the potential to be a novel anti-inflammatory agent for allergic inflammation treatment in the future.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.

ABSTRACT
Newly discovered cell penetration peptides derived from human eosinophil cationic proteins (CPPecp) have the characteristic of cell internalization, but the effect of CPPecp on immunomodulation has not been clarified. House dust mite (HDM) major allergen, Der p 2, can induce proinflammatory cytokine production which contributes to airway inflammation and allergic asthma. However, the mechanism of Der p 2 on NLRP3 inflammasome activation remains unclear. The aim of this study was to investigate the immunomodulatory effect of CPPecp on inhibition of Der p 2 induced inflammasome activation. We showed that proinflammatory cytokines IL-1β, IL-6 and IL-8 were significantly upregulated in peripheral blood mononuclear cells (PBMCs) derived from HDM allergic patients after Der p 2 stimulation. Expression of NLRP3, ASC, Caspase-1, IL-1β and Caspase-1 activity was upregulated in THP-1 cells after Der p 2 stimulation. Proinflammatory cytokine production, NLRP3 inflammasome activation and caspase-1 activity were downregulated in THP-1 cells and CD14+ cells co-cultured with Der p 2 and CPPecp. The immunomodulatory effect of CPPecp was through upregulation of IFN-α production but not induction of autophagy. These results suggested Der p 2 plays an important role in NLRP3 inflammasome activation and CPPecp has the potential to be a novel anti-inflammatory agent for allergic inflammation treatment in the future.

No MeSH data available.


Related in: MedlinePlus