NLRP1 and NLRP3 inflammasomes as a new approach to skin carcinogenesis (Review)

Abstract

Inflammasomes are key innate immune system receptors that detect pathogenic endo-and exogenous stressors like microorganisms or ultraviolet radiation (UVR) which activate the highly proinflammatory cytokines interleukin-1β and interleukin-18. Inflammasomes are not only involved in inflammation, but also in carcinogenesis and tumor progression. Due to the dynamic increase in non-melanoma skin cancers (NMSC), it has become necessary to determine how UVR, which plays a key role in NMSC development, can regulate the structure and function of inflammasomes. In the present study, the regulatory mechanisms of NOD-Like Receptor Family Pyrin Domain Containing 1 and 3 inflammasome activation as well as an effective inflammasome-mediated immune response after UVR exposition are discussed. The differences and similarities between these molecular complexes that monitor cellular health, inflammation, and skin carcinogenesis are also highlighted. Despite numerous scientific data, more studies are still required to better understand the biology of inflammasomes in skin cancer development and to explore their therapeutic potential.

NLRP1 Functions Downstream of the MAPK/ERK Signaling via ATF4 and Contributes to Acquired Targeted Therapy Resistance in Human Metastatic Melanoma

“…The elevated levels of IL-1β secreted from these SK-MEL-28 cells indicate that NLRP inflammasomes are activated in resistant cells, leading to cellular IL-1β processing and release into the extracellular space. NLRP1 and NLRP3 are two key NLRP family members for IL-1β secretion in melanoma [ 12 , 19 ]. Since increased nuclear ATF4 protein ( Figure 3 e and Figure S9 ) and ATF4 gene ( Figure 3 f) expression were seen in drug-resistant cells, we determined ATF4-regulated NLRP1 gene expression.…”

Ultraviolet Radiation and Chronic Inflammation—Molecules and Mechanisms Involved in Skin Carcinogenesis: A Narrative Review

“…UVR can affect the human system both positively and negatively. The advantages of exposure to UVR are primarily the synthesis of vitamin D [19,20]. The harmful properties of ultraviolet radiation include mainly the effects of this factor on the skin in the form of sunburn, photodermatosis, photoaging, and the formation of precancerous and neoplastic skin lesions.…”

Matrix metalloproteinases in keratinocyte carcinomas

“…The expression level of MMP‑1 at mRNA and protein is elevated in BCC tumors compared to unaffected tissue. [ 101 ] MMP‐1 is expressed by stromal fibroblasts, macrophages and in BCC tumor margins, and the expression is more abundant in superficial BCC than in nodular BCC. [ 102,103 ] Moreover, MMP‐1 expression is stronger in invasive morpheaform and recurrent BCC than in superficial, micronodular and cystic BCC, suggesting a role for MMP‐1 in ECM remodelling and tumor invasion in BCC.…”

“…MMP‐9 expression is detected in stromal fibroblasts in the invasive area of infiltrating BCC [ 84,106,109 ] and the mRNA and protein expression level of MMP‑9 is elevated in BCC compared to unaffected tissue. [ 101 ] MMP‐9 is also detected in the BCC tumor epithelium and is associated with inflammatory cell infiltrate in the microenvironment of BCC. [ 84,109 ] MMP‐9 is expressed differently in BCC subtypes, and IHC staining of MMP‐9 is more positive in superficial BCC tumor subtype.…”