Modulation of Lipopolysaccharide‐Induced NF‐κB Signaling Pathway by 635 nm Irradiation via Heat Shock Protein 27 in Human Gingival Fibroblast Cells

Abstract

Heat shock protein-27 (HSP27) is a member of the small HSP family which has been linked to the nuclear factor-kappa B (NF-κB) signaling pathway regulating inflammatory responses. Clinical reports have suggested that low-level light therapy/laser irradiation (LLLT) could be an effective alternative treatment to relieve inflammation during bacterial infection associated with periodontal disease. However, it remains unclear how light irradiation can modulate the NF-κB signaling pathway. We examined whether or not 635 nm irradiation could lead to a modulation of the NF-kB signaling pathway in HSP27-silenced cells and analyzed the functional cross-talk between these factors in NF-κB activation. The results showed that 635 nm irradiation led to a decrease in the HSP27 phosphorylation, reactive oxygen species (ROS) generation, I-κB kinase (IKK)/inhibitor of κB (IκB)/NF-κB phosphorylation, NF-κB p65 translocation and a subsequent decrease in the COX-1/2 expression and prostaglandin (PGE(2) ) release in lipopolysaccharide(LPS)-induced human gingival fibroblast cells (hGFs). However, in HSP27-silenced hGFs, no obvious changes were observed in ROS generation, IKK/IκB/NF-κB phosphorylation, NF-κB p65 translocation, nor in COX-1/2 expression, or PGE(2) release. This could be a mechanism by which 635 nm irradiation modulates LPS-induced NF-κB signaling pathway via HSP27 in inflammation. Thus, HSP27 may play a role in regulating the anti-inflammatory response of LLLT.

Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy

“…However HSP27 plays a negative role in TNF-mediated IκB kinase (IKK) activation. The results of a study performed by Lim and co-workers with HSP27-silenced cells showed that 635 nm light irradiation was not able to decrease ROS generation if HSP27 was not present, indicating that this chaperone plays an important role in ROS decreasing during inflammation and PBM [99]. …”

“…The light irradiation was able to decrease intracellular ROS, which mediate the expression of calcium-dependent phospholipase A2 (cPLA2), secretory phospholipase A2 (sPLA2), and COX-2, and also inhibit the release of PGE2 [99]. …”

“…Lim demonstrated that 635 nm light irradiation suppressed the release of PGE2, possibly through a mechanism related to the inhibition of NF-κB pathway. It did not affect the phosphorylation of IκB, IKK and NF-κB in HSP27-silenced human gingival fibroblasts (hGFs), suggesting that NF-κB modulation by 635 nm light through HSP27 is required for the down-regulation of pro-inflammatory gene expression in these fibroblasts [99]. …”

Photobiomodulation and the brain: a new paradigm

“…Lim et al found that 635 nm light irradiation at low power was able to cause such inhibition by decreasing intracellular ROS. Inhibition of COX-2 via pharmaceutical means is widely supported at current, with COX-2 inhibitors making up a significant portion of the market for non steroidal anti-inflammatory drugs (NSAIDS) [69]. Through PBM, essentially the same result is being accomplished, just with a different stimulus.…”

Pre-Conditioning with Low-Level Laser (Light) Therapy: Light before the Storm

“…One of the unifying Reduction of COX-2 mRNA in rat paw and brain (Prianti et al, 2014) Cytokines (IL10) Upregulation of IL10 in plasma and heart (Cai et al, 2012) Reduced IL6 and TNFa and increased IL10 in muscle of rats with heart failure (Hentschke et al, 2013) Nitric oxide Increases circulating nitrites in mice (Rassaf et al, 2014) Increases venous nitric oxide levels (Mitchell and Mack, 2013) Oxidative stress Reduction of oxidative stress and downregulation of COX-2 expression in rat kidney (Sedaghat et al, 2013) Reduction of oxidative and nitrative stress in injured tibialis anterior muscle in rat (Assis et al, 2012) Heat shock proteins Over-expression of the HSP70i gene in transgenic mice limits infarct size and improves post-ischaemic contractile recovery (Marber et al, 1995) Decrease in the HSP27 phosphorylation thereby decreasing NF-κB p65 translocation human gingival fibroblast cells. (Lim et al, 2013) MAP tyrosine kinase Phosphorylation of p38 MAPK via mitochondria translocation of Bcl-xL in mice brain Increase in MAP kinase activity leading to increase in VEGF levels in human granulosa cells. Kinin receptors Down-regulates kinin receptor expression in neutrophils of patients undergoing heart surgery.…”