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Propionibacterium acnes Induces IL-1β secretion via the NLRP3 inflammasome in human monocytes.

Qin M, Pirouz A, Kim MH, Krutzik SR, Garbán HJ, Kim J - J. Invest. Dermatol. (2013)

Bottom Line: Propionibacterium acnes induction of inflammatory responses is a major etiological factor contributing to the pathogenesis of acne vulgaris.Moreover, silencing of NLRP3, but not NLRP1, expression by small interfering RNA attenuated P. acnes-induced IL-1β secretion.The mechanism of P. acnes-induced NLRP3 activation and subsequent IL-1β secretion was found to involve potassium efflux.

View Article: PubMed Central - PubMed

Affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

ABSTRACT
Propionibacterium acnes induction of inflammatory responses is a major etiological factor contributing to the pathogenesis of acne vulgaris. In particular, the IL-1 family of cytokines has a critical role in both initiation of acne lesions and in the inflammatory response in acne. In this study, we demonstrated that human monocytes respond to P. acnes and secrete mature IL-1β partially via the NLRP3-mediated pathway. When monocytes were stimulated with live P. acnes, caspase-1 and caspase-5 gene expression was upregulated; however, IL-1β secretion required only caspase-1 activity. P. acnes induced key inflammasome genes including NLRP1 and NLPR3. Moreover, silencing of NLRP3, but not NLRP1, expression by small interfering RNA attenuated P. acnes-induced IL-1β secretion. The mechanism of P. acnes-induced NLRP3 activation and subsequent IL-1β secretion was found to involve potassium efflux. Finally, in acne lesions, mature caspase-1 and NLRP3 were detected around the pilosebaceous follicles and colocalized with tissue macrophages. Taken together, our results indicate that P. acnes triggers a key inflammatory mediator, IL-1β, via NLRP3 and caspase-1 activation, suggesting a role for inflammasome-mediated inflammation in acne pathogenesis.

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Related in: MedlinePlus

P. acnes induction of IL-1β is NLRP3-dependent in human monocytesa) Monocytes were stimulated with P. acnes (MOI 0.5) and the gene expression of major NLRs was determined after 24 hours using RT-PCR. Data is representative of four independent experiments; b) Monocytes were transfected with siRNA oligos specific for NLRP3, NLRP1 or a non-specific siRNA oligo (siCTRL) prior to stimulations with P. acnes (MOI 0.5) and the levels of NLRP3 and NLRP1 were assessed by qRT-PCR and are represented as fold change versus media control; and c) siRNA transfected cells were then stimulated with P. acnes (MOI of 0.5) then culture supernatants were collected after 24 hours and assayed with IL-1β ELISA (n=3; ** p ≤ 0.01).
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Figure 3: P. acnes induction of IL-1β is NLRP3-dependent in human monocytesa) Monocytes were stimulated with P. acnes (MOI 0.5) and the gene expression of major NLRs was determined after 24 hours using RT-PCR. Data is representative of four independent experiments; b) Monocytes were transfected with siRNA oligos specific for NLRP3, NLRP1 or a non-specific siRNA oligo (siCTRL) prior to stimulations with P. acnes (MOI 0.5) and the levels of NLRP3 and NLRP1 were assessed by qRT-PCR and are represented as fold change versus media control; and c) siRNA transfected cells were then stimulated with P. acnes (MOI of 0.5) then culture supernatants were collected after 24 hours and assayed with IL-1β ELISA (n=3; ** p ≤ 0.01).

Mentions: In order to identify the specific inflammasome involved in P. acnes induction of IL-1β, we first analyzed the gene expression of major NLRs by RT-PCR in monocytes treated with or without P. acnes. Our results show that P. acnes induces gene expression of NLRP1 and NLRP3 in human monocytes (Fig. 3a). In contrast, AIM2 and IPAF were expressed in unstimulated monocytes and their expression was not affected by P. acnes treatment (Fig. 3a).


Propionibacterium acnes Induces IL-1β secretion via the NLRP3 inflammasome in human monocytes.

Qin M, Pirouz A, Kim MH, Krutzik SR, Garbán HJ, Kim J - J. Invest. Dermatol. (2013)

P. acnes induction of IL-1β is NLRP3-dependent in human monocytesa) Monocytes were stimulated with P. acnes (MOI 0.5) and the gene expression of major NLRs was determined after 24 hours using RT-PCR. Data is representative of four independent experiments; b) Monocytes were transfected with siRNA oligos specific for NLRP3, NLRP1 or a non-specific siRNA oligo (siCTRL) prior to stimulations with P. acnes (MOI 0.5) and the levels of NLRP3 and NLRP1 were assessed by qRT-PCR and are represented as fold change versus media control; and c) siRNA transfected cells were then stimulated with P. acnes (MOI of 0.5) then culture supernatants were collected after 24 hours and assayed with IL-1β ELISA (n=3; ** p ≤ 0.01).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4116307&req=5

Figure 3: P. acnes induction of IL-1β is NLRP3-dependent in human monocytesa) Monocytes were stimulated with P. acnes (MOI 0.5) and the gene expression of major NLRs was determined after 24 hours using RT-PCR. Data is representative of four independent experiments; b) Monocytes were transfected with siRNA oligos specific for NLRP3, NLRP1 or a non-specific siRNA oligo (siCTRL) prior to stimulations with P. acnes (MOI 0.5) and the levels of NLRP3 and NLRP1 were assessed by qRT-PCR and are represented as fold change versus media control; and c) siRNA transfected cells were then stimulated with P. acnes (MOI of 0.5) then culture supernatants were collected after 24 hours and assayed with IL-1β ELISA (n=3; ** p ≤ 0.01).
Mentions: In order to identify the specific inflammasome involved in P. acnes induction of IL-1β, we first analyzed the gene expression of major NLRs by RT-PCR in monocytes treated with or without P. acnes. Our results show that P. acnes induces gene expression of NLRP1 and NLRP3 in human monocytes (Fig. 3a). In contrast, AIM2 and IPAF were expressed in unstimulated monocytes and their expression was not affected by P. acnes treatment (Fig. 3a).

Bottom Line: Propionibacterium acnes induction of inflammatory responses is a major etiological factor contributing to the pathogenesis of acne vulgaris.Moreover, silencing of NLRP3, but not NLRP1, expression by small interfering RNA attenuated P. acnes-induced IL-1β secretion.The mechanism of P. acnes-induced NLRP3 activation and subsequent IL-1β secretion was found to involve potassium efflux.

View Article: PubMed Central - PubMed

Affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

ABSTRACT
Propionibacterium acnes induction of inflammatory responses is a major etiological factor contributing to the pathogenesis of acne vulgaris. In particular, the IL-1 family of cytokines has a critical role in both initiation of acne lesions and in the inflammatory response in acne. In this study, we demonstrated that human monocytes respond to P. acnes and secrete mature IL-1β partially via the NLRP3-mediated pathway. When monocytes were stimulated with live P. acnes, caspase-1 and caspase-5 gene expression was upregulated; however, IL-1β secretion required only caspase-1 activity. P. acnes induced key inflammasome genes including NLRP1 and NLPR3. Moreover, silencing of NLRP3, but not NLRP1, expression by small interfering RNA attenuated P. acnes-induced IL-1β secretion. The mechanism of P. acnes-induced NLRP3 activation and subsequent IL-1β secretion was found to involve potassium efflux. Finally, in acne lesions, mature caspase-1 and NLRP3 were detected around the pilosebaceous follicles and colocalized with tissue macrophages. Taken together, our results indicate that P. acnes triggers a key inflammatory mediator, IL-1β, via NLRP3 and caspase-1 activation, suggesting a role for inflammasome-mediated inflammation in acne pathogenesis.

Show MeSH
Related in: MedlinePlus