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Benzalkonium chloride (BAC) exposure activates interleukin-6 (IL-6) trans-signaling and downstream inflammatory responses in human telomerase-immortalized corneal epithelial (hTCEpi) cells. a , b The sIL-6R/sgp130 ratio and secreted IL-6 protein levels were significantly increased in the conditioned media of BAC-treated hTCEpi cells as compared with untreated controls. c , d BAC-induced increases in IL6 and IL6RA gene expression were significantly attenuated by selective inhibition of IL-6 trans-signaling with sgp130Fc, indicating partial protection against these effects. e , f Similarly, sgp130Fc partially prevented BAC-induced upregulation of monocyte chemoattractant protein 1 ( MCP1 ) and intercellular adhesion molecule 1 (ICAM1) gene expression. Data are represented as mean ± standard error of the mean, n = 3–30/group; * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Journal: Eye and Vision

Article Title: Blocking IL-6 trans-signaling mitigates benzalkonium chloride-induced inflammation, oxidative imbalance, ER stress, and barrier disruption in human corneal epithelial cells

doi: 10.1186/s40662-026-00513-0

Figure Lengend Snippet: Benzalkonium chloride (BAC) exposure activates interleukin-6 (IL-6) trans-signaling and downstream inflammatory responses in human telomerase-immortalized corneal epithelial (hTCEpi) cells. a , b The sIL-6R/sgp130 ratio and secreted IL-6 protein levels were significantly increased in the conditioned media of BAC-treated hTCEpi cells as compared with untreated controls. c , d BAC-induced increases in IL6 and IL6RA gene expression were significantly attenuated by selective inhibition of IL-6 trans-signaling with sgp130Fc, indicating partial protection against these effects. e , f Similarly, sgp130Fc partially prevented BAC-induced upregulation of monocyte chemoattractant protein 1 ( MCP1 ) and intercellular adhesion molecule 1 (ICAM1) gene expression. Data are represented as mean ± standard error of the mean, n = 3–30/group; * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: The following primary antibodies were used: PRDX (1:100, #sc-137222, Santa Cruz Biotechnology), Catalase (1:250, #sc-271803, Santa Cruz Biotechnology), BiP (1:1000, #A0241, ABclonal), PERK (1:1000, #5683, Cell Signaling), Ero1α (1:1000, #3264, Cell Signaling), β-catenin (1:500, #8480S, Cell Signaling), Occludin (1:200, #40–4700, Invitrogen), Claudin-1 (1:1000, #A2196, ABclonal), IL-6R (1:1000, #A1570, ABclonal), gp130 (1:100, #sc-655, Santa Cruz Biotechnology), and β-actin (1:10,000, #AC028, ABclonal).

Techniques: Gene Expression, Inhibition

Proposed molecular mechanisms of interleukin-6 (IL-6) trans-signaling in benzalkonium chloride (BAC)-induced corneal epithelial dysfunction. BAC impairs corneal epithelial barrier integrity while promoting inflammation, oxidative imbalance, ER stress, and junctional protein loss partially through an IL-6 trans-signaling-dependent mechanism. Selective inhibition of IL-6 trans-signaling with sgp130Fc attenuates these pathological changes. BiP, binding immunoglobulin protein; CAT, catalase; Ero1α, endoplasmic reticulum oxidoreductase 1 alpha; GPX, glutathione peroxidase; HSP72, heat shock protein 72; ICAM1, intercellular adhesion molecule 1; MCP1, monocyte chemoattractant protein 1; mIL-6R, membrane-bound IL-6 receptor; PERK, protein kinase RNA-like endoplasmic reticulum kinase; PRDX, peroxiredoxin; ROS, reactive oxygen species; sIL-6R, soluble IL-6 receptor; SOD1, superoxide dismutase 1; TER, trans-epithelial electrical resistance; TXN, thioredoxin

Journal: Eye and Vision

Article Title: Blocking IL-6 trans-signaling mitigates benzalkonium chloride-induced inflammation, oxidative imbalance, ER stress, and barrier disruption in human corneal epithelial cells

doi: 10.1186/s40662-026-00513-0

Figure Lengend Snippet: Proposed molecular mechanisms of interleukin-6 (IL-6) trans-signaling in benzalkonium chloride (BAC)-induced corneal epithelial dysfunction. BAC impairs corneal epithelial barrier integrity while promoting inflammation, oxidative imbalance, ER stress, and junctional protein loss partially through an IL-6 trans-signaling-dependent mechanism. Selective inhibition of IL-6 trans-signaling with sgp130Fc attenuates these pathological changes. BiP, binding immunoglobulin protein; CAT, catalase; Ero1α, endoplasmic reticulum oxidoreductase 1 alpha; GPX, glutathione peroxidase; HSP72, heat shock protein 72; ICAM1, intercellular adhesion molecule 1; MCP1, monocyte chemoattractant protein 1; mIL-6R, membrane-bound IL-6 receptor; PERK, protein kinase RNA-like endoplasmic reticulum kinase; PRDX, peroxiredoxin; ROS, reactive oxygen species; sIL-6R, soluble IL-6 receptor; SOD1, superoxide dismutase 1; TER, trans-epithelial electrical resistance; TXN, thioredoxin

Article Snippet: The following primary antibodies were used: PRDX (1:100, #sc-137222, Santa Cruz Biotechnology), Catalase (1:250, #sc-271803, Santa Cruz Biotechnology), BiP (1:1000, #A0241, ABclonal), PERK (1:1000, #5683, Cell Signaling), Ero1α (1:1000, #3264, Cell Signaling), β-catenin (1:500, #8480S, Cell Signaling), Occludin (1:200, #40–4700, Invitrogen), Claudin-1 (1:1000, #A2196, ABclonal), IL-6R (1:1000, #A1570, ABclonal), gp130 (1:100, #sc-655, Santa Cruz Biotechnology), and β-actin (1:10,000, #AC028, ABclonal).

Techniques: Inhibition, Binding Assay, Membrane

( A ) The schematic protocol for anti–IL-6 treatment. ( B ) Ankle thickness after the intervention. ( C ) Ankle thickness at day 24. ( D ) Representative histology. ( E ) Cumulative data of the histological score. (B to E) N = 7 to 11 from four independent experiments. ( F ) The potential to flare arthritis by IL-6. The illustration shows how the mice were treated. ( G ) Ankle thickness after the intervention. ( H ) Ankle thickness at day 24. ( I ) Representative histology. ( J ) Cumulative data of the histological score. (G to J) N = 8 to 9 from two independent experiments. P values were determined by unpaired t test.

Journal: Science Advances

Article Title: Fibroblast-like synoviocytes exacerbate autoimmune arthritis upon psychological stress in an IL-6–dependent manner

doi: 10.1126/sciadv.aec9257

Figure Lengend Snippet: ( A ) The schematic protocol for anti–IL-6 treatment. ( B ) Ankle thickness after the intervention. ( C ) Ankle thickness at day 24. ( D ) Representative histology. ( E ) Cumulative data of the histological score. (B to E) N = 7 to 11 from four independent experiments. ( F ) The potential to flare arthritis by IL-6. The illustration shows how the mice were treated. ( G ) Ankle thickness after the intervention. ( H ) Ankle thickness at day 24. ( I ) Representative histology. ( J ) Cumulative data of the histological score. (G to J) N = 8 to 9 from two independent experiments. P values were determined by unpaired t test.

Article Snippet: For IL-6 signal blocking, either 200 μg of rat IgG2b isotype control antibody or anti–IL-6R antibody (15A7, BioXCell) was intraperitoneally injected before the first and third tube restraint procedures.

Techniques: Histology