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p38 MAP Kinase Inhibition Reduces Propionibacterium acnes-Induced Inflammation in Vitro.

Li WH, Zhang L, Lyte P, Rodriguez K, Cavender D, Southall MD - Dermatol Ther (Heidelb) (2015)

Bottom Line: Furthermore, SCIO-469, a selective inhibitor of p38α, showed similar effects in cultured keratinocytes.Topical treatment of SCIO-469 inhibited the P. acnes-induced phospho-p38 and cytokine secretion in human epidermal equivalents.Johnson & Johnson.

View Article: PubMed Central - PubMed

Affiliation: Department of Skin Biology and Pharmacology, The Johnson & Johnson Skin Research Center, Johnson & Johnson Consumer and Personal Products Worldwide, Division of Johnson and Johnson Consumer Companies, Inc., 199 Grandview Road, Skillman, NJ, 08558, USA, whli@its.jnj.com.

ABSTRACT

Introduction: Propionibacterium acnes, a ubiquitous skin bacterium, stimulates keratinocytes to produce a number of proinflammatory cytokines and may contribute to inflammatory acne. The aim of the study was to investigate whether P. acnes-induced proinflammatory cytokine release is mediated by P. acnes-induced activation of p38 mitogen-activated protein kinase (p38 MAPK or p38) in human keratinocytes.

Methods: Immunohistochemistry was used to evaluate p38 phosphorylation in human skin samples with or without acne. Primary human keratinocytes and epidermal skin equivalents were exposed to viable P. acnes. Phosphorylation of MAPKs without or with p38 inhibitors was examined by Western blot and cytokine secretion was detected by Enzyme-Linked Immunosorbent Assay (ELISA).

Results: Increased levels of phospho-p38 were observed in human acne lesions, predominantly in follicular and perifollicular keratinocytes. Exposure of cultured human keratinocytes to viable P. acnes resulted in phosphorylation of multiple members of the MAPK family, including rapid and transient activation of p38 and extracellular signal-related kinase (ERK1/2) and relatively slow but sustained activation of c-Jun N-terminal kinases (JNK1/2). Viable P. acnes induced the secretion of interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), and IL-8 from human keratinocytes. The phosphorylation of p38 (phospho-p38) and the secretion of cytokines induced by P. acnes in cultured keratinocytes were inhibited by SB203580, a p38α/β inhibitor. Furthermore, SCIO-469, a selective inhibitor of p38α, showed similar effects in cultured keratinocytes. Topical treatment of SCIO-469 inhibited the P. acnes-induced phospho-p38 and cytokine secretion in human epidermal equivalents.

Conclusion: The data demonstrate that P. acnes induces p38-dependent inflammatory responses in keratinocytes, and suggest that p38 may play an important role in the pathogenesis of inflammatory acne.

Funding: Johnson & Johnson.

No MeSH data available.


Related in: MedlinePlus

Propionibacterium acnes induces activation of multiple MAPK pathways in cultured human keratinocytes. a Western blots show time-dependent induction of phospho-p38 (p-p38), phospho-ERK1/2 (p-ERK1/2) and phospho-JNK1/2 (p-JNK1/2). b–d The density of each phosphorylated MAPK band was normalized to its loading control, and then compared to time 0. MAPK mitogen-activated protein kinase, ERK extracellular signal-related kinases, JNK c-Jun N-terminal kinases
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Fig2: Propionibacterium acnes induces activation of multiple MAPK pathways in cultured human keratinocytes. a Western blots show time-dependent induction of phospho-p38 (p-p38), phospho-ERK1/2 (p-ERK1/2) and phospho-JNK1/2 (p-JNK1/2). b–d The density of each phosphorylated MAPK band was normalized to its loading control, and then compared to time 0. MAPK mitogen-activated protein kinase, ERK extracellular signal-related kinases, JNK c-Jun N-terminal kinases

Mentions: Stationary-phase P. acnes stimulated rapid (within 5 min) phosphorylation of both p38 (phospho-p38) and ERK1/2 (phospho-ERK1/2), with peaks at 15 min (Fig. 2a). There was up to a sevenfold increase in phosphorylation of p38 and ERK1/2, compared to untreated (Fig. 2b, c). An additional activation peak of phospho-ERK1/2 occurred between 2 and 4 h (approximately sixfold increase; Fig. 2a, c). P. acnes also induced relatively slow but sustained phosphorylation of JNK1/2 (phospho-JNK1/2); the maximum increase was approximately fourfold between 2 and 8 h (Fig. 2a, d). These results show that viable P. acnes induced the activation of multiple MAPK pathways in cultured human keratinocytes.Fig. 2


p38 MAP Kinase Inhibition Reduces Propionibacterium acnes-Induced Inflammation in Vitro.

Li WH, Zhang L, Lyte P, Rodriguez K, Cavender D, Southall MD - Dermatol Ther (Heidelb) (2015)

Propionibacterium acnes induces activation of multiple MAPK pathways in cultured human keratinocytes. a Western blots show time-dependent induction of phospho-p38 (p-p38), phospho-ERK1/2 (p-ERK1/2) and phospho-JNK1/2 (p-JNK1/2). b–d The density of each phosphorylated MAPK band was normalized to its loading control, and then compared to time 0. MAPK mitogen-activated protein kinase, ERK extracellular signal-related kinases, JNK c-Jun N-terminal kinases
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4374066&req=5

Fig2: Propionibacterium acnes induces activation of multiple MAPK pathways in cultured human keratinocytes. a Western blots show time-dependent induction of phospho-p38 (p-p38), phospho-ERK1/2 (p-ERK1/2) and phospho-JNK1/2 (p-JNK1/2). b–d The density of each phosphorylated MAPK band was normalized to its loading control, and then compared to time 0. MAPK mitogen-activated protein kinase, ERK extracellular signal-related kinases, JNK c-Jun N-terminal kinases
Mentions: Stationary-phase P. acnes stimulated rapid (within 5 min) phosphorylation of both p38 (phospho-p38) and ERK1/2 (phospho-ERK1/2), with peaks at 15 min (Fig. 2a). There was up to a sevenfold increase in phosphorylation of p38 and ERK1/2, compared to untreated (Fig. 2b, c). An additional activation peak of phospho-ERK1/2 occurred between 2 and 4 h (approximately sixfold increase; Fig. 2a, c). P. acnes also induced relatively slow but sustained phosphorylation of JNK1/2 (phospho-JNK1/2); the maximum increase was approximately fourfold between 2 and 8 h (Fig. 2a, d). These results show that viable P. acnes induced the activation of multiple MAPK pathways in cultured human keratinocytes.Fig. 2

Bottom Line: Furthermore, SCIO-469, a selective inhibitor of p38α, showed similar effects in cultured keratinocytes.Topical treatment of SCIO-469 inhibited the P. acnes-induced phospho-p38 and cytokine secretion in human epidermal equivalents.Johnson & Johnson.

View Article: PubMed Central - PubMed

Affiliation: Department of Skin Biology and Pharmacology, The Johnson & Johnson Skin Research Center, Johnson & Johnson Consumer and Personal Products Worldwide, Division of Johnson and Johnson Consumer Companies, Inc., 199 Grandview Road, Skillman, NJ, 08558, USA, whli@its.jnj.com.

ABSTRACT

Introduction: Propionibacterium acnes, a ubiquitous skin bacterium, stimulates keratinocytes to produce a number of proinflammatory cytokines and may contribute to inflammatory acne. The aim of the study was to investigate whether P. acnes-induced proinflammatory cytokine release is mediated by P. acnes-induced activation of p38 mitogen-activated protein kinase (p38 MAPK or p38) in human keratinocytes.

Methods: Immunohistochemistry was used to evaluate p38 phosphorylation in human skin samples with or without acne. Primary human keratinocytes and epidermal skin equivalents were exposed to viable P. acnes. Phosphorylation of MAPKs without or with p38 inhibitors was examined by Western blot and cytokine secretion was detected by Enzyme-Linked Immunosorbent Assay (ELISA).

Results: Increased levels of phospho-p38 were observed in human acne lesions, predominantly in follicular and perifollicular keratinocytes. Exposure of cultured human keratinocytes to viable P. acnes resulted in phosphorylation of multiple members of the MAPK family, including rapid and transient activation of p38 and extracellular signal-related kinase (ERK1/2) and relatively slow but sustained activation of c-Jun N-terminal kinases (JNK1/2). Viable P. acnes induced the secretion of interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), and IL-8 from human keratinocytes. The phosphorylation of p38 (phospho-p38) and the secretion of cytokines induced by P. acnes in cultured keratinocytes were inhibited by SB203580, a p38α/β inhibitor. Furthermore, SCIO-469, a selective inhibitor of p38α, showed similar effects in cultured keratinocytes. Topical treatment of SCIO-469 inhibited the P. acnes-induced phospho-p38 and cytokine secretion in human epidermal equivalents.

Conclusion: The data demonstrate that P. acnes induces p38-dependent inflammatory responses in keratinocytes, and suggest that p38 may play an important role in the pathogenesis of inflammatory acne.

Funding: Johnson & Johnson.

No MeSH data available.


Related in: MedlinePlus