NLRP1 Is the Key Inflammasome in Primary Human Keratinocytes

Burian, Marc; Yazdi, Amir S.

doi:10.1016/j.jid.2018.08.004

Cited by 44 publications

(42 citation statements)

References 12 publications

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“…Further discovery that NLRP1 and NLRP3 inflammasomes are both expressed in skin keratinocytes and respond to skin wounding and UV radiation damage demonstrates that these key skin cells, creating the first line of living defense against exogenous attack, are critical for maintaining the health of the skin. 42,43 In this work, the activation of keratinocytes by two known Inflammasome activators, ATP and UVB, was confirmed via testing for direct expression of ACasp-1 in exposed cells. It was surprising that MCC950, a known inflammasome inhibitor, had little impact on either ATP or UVB expression of ACasp-1 in these assays.…”

Section: Discussionmentioning

confidence: 59%

“…40 Normal human epidermal keratinocytes (NHEK) have been shown to express Caspase-1 through NLR protein cascades. 35,[41][42][43] However, there is ongoing examination and discussion if the NLRP1 or NLRP3 inflammasome pathways are the most critical to skin health. 42,43 This paper will discuss efforts to examine the expression of Caspase-1 from externally stressed NHEKs.…”

Section: Caspase-1: a Measure Of Nlrp Inflammasome Activationmentioning

confidence: 99%

“…35,[41][42][43] However, there is ongoing examination and discussion if the NLRP1 or NLRP3 inflammasome pathways are the most critical to skin health. 42,43 This paper will discuss efforts to examine the expression of Caspase-1 from externally stressed NHEKs. In addition, the paper will examine the ability of some selected polysaccharide-and antioxidant-based topical treatments to inhibit Caspase-1 expression in Inflammasome-activated keratinocytes.…”

Section: Caspase-1: a Measure Of Nlrp Inflammasome Activationmentioning

confidence: 99%

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<p>In vitro expression of NLRP inflammasome-induced active Caspase-1 expression in normal human epidermal keratinocytes (NHEK) by various exogenous threats and subsequent inhibition by naturally derived ingredient blends</p>

Gruber¹,

Holtz²

2019

JIR

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Background: The discovery of the nod-like receptor protein (NLRP) inflammasomes in 2002 has led to the rapid identification of these unique cellular proteins as key targets for studies on innate inflammation pathways. The NLRP inflammasomes have been shown to be expressed in normal human epidermal keratinocytes (NHEK) and human dermal fibroblasts (HDF). NLRP inflammasomes in keratinocytes are interesting as these skin cells are the first living cells in the skin to contact external exogenous threats such as UV energy, chemicals, physical trauma, and bacteria and viruses. Activation of the NLRP Inflammasomes by exogenous threats results in the release of active Caspase-1 (ACasp-1), a key protease enzyme, which targets inactive forms of IL-1β, IL-18 as well as IL-1α and IL-33. Purpose: This article discusses efforts to examine the release of active Caspase-1 from NHEKs activated by various exogenous threats including UVB energy, ATP, Nigericin and Urban Dust. The work further examines if, after inflammasome activation and Caspase-1 release, certain naturally derived botanical ingredients known to have anti-inflammatory effects can function to inhibit upregulation of active Caspase-1. Methods: NHEK were treated with various doses of UVB, ATP and Nigericin and with a single dose of Urban Dust. ACasp-1 expression was measured after 3 and 20 hours using the Promega Caspase Glo-1 bioluminescent assay. After confirmation that 60 mJ/cm 2 of UVB and 5mM of ATP were effective to activate NHEK ACasp-1 release after 20 hrs, these conditions were employed to examine the influence of three botanical blends of ingredients on their ability to inhibit ACasp-1 expression. Results: Initial results demonstrate that NHEKs can be activated to release active Caspase-1 by ATP and UVB, but not by Nigericin or Urban Dust. In addition, it was unexpectedly found that, while ATP and UVB activated NHEKs, the release of ACasp-1-did not happen within the first 3 hours after exposure but did become significant after 20 hours. Additional results indicate that a blend of polysaccharides and two blends of antioxidants, one oilsoluble and the other water-soluble, known for their anti-inflammatory effects, can reduce expression of active Caspase-1 in activated NHEKs when applied extracellularly. Conclusion: Expression of NLRP activated release of ACasp-1 was found to be influenced by UVB and ATP but not by Nigericin or Urban Dust. The effects were also time dependent. Several botanical extract blends were found to reduce ACasp-1 expression in previously activated NHEKs. Links between these inflammatory effects and processes of cellular inflammaging are discussed.

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Section: Discussionmentioning

confidence: 59%

Section: Caspase-1: a Measure Of Nlrp Inflammasome Activationmentioning

confidence: 99%

Section: Caspase-1: a Measure Of Nlrp Inflammasome Activationmentioning

confidence: 99%

See 1 more Smart Citation

<p>In vitro expression of NLRP inflammasome-induced active Caspase-1 expression in normal human epidermal keratinocytes (NHEK) by various exogenous threats and subsequent inhibition by naturally derived ingredient blends</p>

Gruber¹,

Holtz²

2019

JIR

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“…33 Various pattern recognition receptors, including Toll-like receptors on the cell membrane and NLRs in the cytoplasm, are expressed in keratinocytes. [34][35][36] The current study focused on the function of NLRP3, a cytoplasmic NLR that is a vital component of the inflammasome, in the innate immunity formed by keratinocytes in patients with vitiligo. We observed pronounced upregulation of NLRP3 and IL-1b in perilesional keratinocytes of patients with vitiligo, which is in agreement with earlier findings that the mRNA or protein levels of IL-1b were increased in lesions or perilesions of patients with vitiligo, 37,38 suggesting a critical role of NLRP3 inflammasome activation in patients with vitiligo.…”

Section: Discussionmentioning

confidence: 99%

Activated NLR family pyrin domain containing 3 (NLRP3) inflammasome in keratinocytes promotes cutaneous T-cell response in patients with vitiligo

Kang

Zhang

et al. 2020

Journal of Allergy and Clinical Immunology

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Background: Keratinocytes can function as innate immune cells under oxidative stress and aggravate the cutaneous T-cell response that undermines melanocytes in the setting of vitiligo. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a regulator of innate immunity that exists in keratinocytes. However, the role of the NLRP3 inflammasome in the pathogenesis of vitiligo has not been investigated. Objective: We sought to explicate the contribution of the activated NLRP3 inflammasome in keratinocytes to the autoimmune response in patients with vitiligo.Methods: Perilesional and serum samples from patients with vitiligo were collected to examine the status of the NLRP3 inflammasome in the setting of vitiligo. Cultured keratinocytes were treated with H 2 O 2 to investigate the mechanism for NLRP3 inflammasome activation under oxidative stress. Peripheral blood T cells were extracted from patients with vitiligo to explore the influence of the NLRP3 inflammasome on the T-cell response in patients with vitiligo. Results: Expressions of NLRP3 and downstream cytokine IL-1b were consistently increased in perilesional keratinocytes of patients with vitiligo. Notably, serum IL-1b levels were From a

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“…Studies have examined the role of the NLRP Inflammasomes in skin health through their action in keratinocytes . These recent discussions are focused on determining whether it is the NLRP1 or NLRP3 inflammasomes that are most responsible for skin health.…”

Section: Introductionmentioning

confidence: 99%

NLRP inflammasomes and induced skin inflammation, barrier recovery and extended skin hydration

Gruber

Stojkoska

2019

Intern J of Cosmetic Sci

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NLRP1 Is the Key Inflammasome in Primary Human Keratinocytes

Cited by 44 publications

References 12 publications

<p>In vitro expression of NLRP inflammasome-induced active Caspase-1 expression in normal human epidermal keratinocytes (NHEK) by various exogenous threats and subsequent inhibition by naturally derived ingredient blends</p>

<p>In vitro expression of NLRP inflammasome-induced active Caspase-1 expression in normal human epidermal keratinocytes (NHEK) by various exogenous threats and subsequent inhibition by naturally derived ingredient blends</p>

Activated NLR family pyrin domain containing 3 (NLRP3) inflammasome in keratinocytes promotes cutaneous T-cell response in patients with vitiligo

NLRP inflammasomes and induced skin inflammation, barrier recovery and extended skin hydration

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