Natural Sulfurs Inhibit LPS-Induced Inflammatory Responses through NF-κB Signaling in CCD-986Sk Skin Fibroblasts

Abstract

Lipopolysaccharide (LPS)-induced inflammatory response leads to serious damage, up to and including tumorigenesis. Natural mineral sulfur, non-toxic sulfur (NTS), and methylsulfonylmethane (MSM) have anti-inflammatory activity that may inhibit LPS-induced inflammation. We hypothesized that sulfur compounds could inhibit LPS-induced inflammatory responses in CCD-986Sk skin fibroblasts. We used Western blotting and real-time PCR to analyze molecular signaling in treated and untreated cultures. We also used flow cytometry for cell surface receptor analysis, comet assays to evaluate DNA damage, and ELISA-based cytokine detection. LPS induced TLR4 activation and NF-κB signaling via canonical and protein kinase C (PKC)-dependent pathways, while NTS and MSM downregulated that response. NTS and MSM also inhibited LPS-induced nuclear accumulation and binding of NF-κB to proinflammatory cytokines COX-2, IL-1β, and IL-6. Finally, the sulfur compounds suppressed LPS-induced ROS accumulation and DNA damage in CCD-986Sk cells. These results suggest that natural sulfur compounds could be used to treat inflammation and may be useful in the development of cosmetics.

The Impact of Inflammatory Stimuli on Xylosyltransferase-I Regulation in Primary Human Dermal Fibroblasts

“…Thus, it can be concluded that fibroblasts are quite resistant to the noxious stimuli that have previously been shown to induce apoptosis in other cell types [ 42 , 43 ]. Consistent with our data, the resistance of human fibroblasts towards exogenous LPS was demonstrated in numerous studies utilizing LPS concentrations ranging up to 10 μg/mL and incubation periods of 48 to 72 h [ 4 , 6 , 38 ]. This highlights the key role of fibroblasts as immune sentinel cells affecting both the inflammatory and repair processes during wound healing and tissue homoeostasis.…”

“…Human fibroblasts regulate the inflammatory response via the toll-like receptor 4 activated by LPS, which led to the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor activation, and cytokine and chemokine expression, including interleukin (IL)-1β and IL-8, resulting in immune cell recruitment and local tissue inflammation [ 3 , 4 ]. The IL-1β is induced by LPS in human fibroblasts with major roles in inflammation, innate immune response and fibrosis [ 5 , 6 ]. Excess production of IL-1β can be detrimental to the host; therefore, its production is closely controlled at various levels to assure its proper release.…”

Secondary Metabolite Profile and Pharmacological Opportunities of Lettuce Plants following Selenium and Sulfur Enhancement

“…The results in the present study indicate that adequate or increased S supply under Se-deficient conditions increases the NO inhibitory potential in green lettuce, as extracts inhibited up to 50% of NO production at concentrations of 106.1 ± 2.4 and 101.0 ± 0.6 µg/mL, respectively (Figure 4). This can be attributed to the known fact that natural S possesses antiinflammatory activity [48]. For instance, organosulfur compounds from garlic eliminated the formation of NO and prostaglandin E2, in addition to their suppressive effect of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6 in lipopolysaccharide-activated macrophages [7].…”

Inhibition of LPS-Induced Skin Inflammatory Response and Barrier Damage via MAPK/NF-κB Signaling Pathway by Houttuynia cordata Thunb Fermentation Broth

“…When the skin is stimulated by external harmful factors, its own barrier function will be compromised. This, in turn, triggers a series of immune responses that help maintain the skin's structure and function by modifying intercellular molecular signaling processes and facilitating matrix remodeling [22]. Low doses of nitric oxide (NO) have many functions, such as promoting wound healing and exhibiting antimicrobial effects against bacterial pathogens.…”