Pyrroloquinoline Quinone Disodium (PQQ2Na) Has an NLRP Inflammasome-Induced Caspase-1 Release Influence in UVB-Irradiated but Not ATP-Treated Human Keratinocytes but Has No Influence in Increasing Skin Cell Mitochondrial Biogenesis in Either Human Keratinocytes or Fibroblasts

Abstract

Introduction: Pyrroloquinoline quinone is a bacterial-derived redox factor that has been shown to have numerous benefits in humans. Recently, a model for examining the ability of normal human epidermal keratinocytes (NHEKs) to demonstrate anti-inflammatory benefits via nod-like receptor protein (NLRP)-activated caspase-1 release was reported. The question of whether PQQ2Na might have anti-inflammatory benefits that function through NLRP-activated release of active caspase-1 has not been explored. In addition, it has been reported that PQQ2Na will induce mitochondrial biogenesis in humans when taken orally. Whether or not this effect occurs in skin cells is presently unknown.

Methods: The inflammation studies followed previously published methods that demonstrated both UVB and ATP were able to upregulate the NLRP-activated release of caspase-1 in NHEKs. In addition, NHEK and normal dermal human fibroblasts (NHDF) were treated with PQQ2Na to see if the molecule might stimulate mitochondrial biogenesis measured by increased expression of cyclooxygenase-1 (COX-1) and succinate dehydrogenase complex, subunit A (SDHA).

Results: At non-cytotoxic concentrations between 5 µg/mL and 100 µg/mL in NHEKs and between 0.1 µg/mL and 5 µg/mL in fibroblasts, the PQQ2Na had no influence on cellular mitochondrial biogenesis. In ATP-activated NHEKs at concentrations of PQQ2Na between 0.05 µg/mL and 50 µg/mL, there was no influence of PQQ2Na on release of active caspase-1. In NHEKs irradiated with 60mJ/cm² of UVB radiation as previously described and treated with 0.05 µg/mL to 50 µg/mL of PQQ2Na, the molecule showed a dose-dependent benefit at reducing the expression of active caspase-1 in the irradiated cells.

Discussion: Benefits of PQQ2Na on various skin cell types which had not been investigated previously were addressed. Surprisingly, the PPQ2Na had no apparent influence on skin cell mitochondrial biogenesis. However, the molecule has a strong suppressing influence on UVB-induced active caspase-1 release in UVB-irradiated NHEKs.

Keywords: caspase-1; inflammasomes; inflammation; mitochondrial biogenesis; pyrroloquinoline quinone disodium.