Table 1.
Tofacitinib effects on the expression of inflammatory molecules induced by IFN-γ in keratinocytes.
| Untreated∗ | TOF | IFN-γ | IFN-γ + TOF | |
|---|---|---|---|---|
| Membrane molecules | ||||
| ICAM1 | 2.4 ± 0.2 | 2.0 ± 0.18 | 75.5 ± 6.3 | 6.8 ± 0.56† |
| HLA-DR | 1.4 ± 0.15 | 1.4 ± 0.12 | 3.5 ± 0.25 | 1.4 ± 0.13† |
| MHC-I | 72 ± 5.2 | 63 ± 4.5 | 146 ± 11.2 | 84 ± 7.4† |
| Chemokines | ||||
| CX3CL1 | 0.40 ± 0.05 | 0.36 ± 0.08 | 580.64 ± 55.06 | 26.20 ± 3.26† |
| CXCL1 | 0.80 ± 0.12 | 0.80 ± 0.07 | 69.00 ± 5.6 | 0.40 ± 0.08† |
| CXCL8 | 0.92 ± 0.11 | 2.60 ± 0.32 | 84.52 ± 7.45 | 5.04 ± 0.61† |
| CXCL10 | 29.08 ± 2.2 | 25.04 ± 0.14 | 2557.44 ± 150.2 | 29.08 ± 2.58† |
| CXCL12 | 107.20 ± 9.72 | 110.20 ± 2.43 | 141.52 ± 12.25 | 119.12 ± 10.61 |
| CXCL16 | 2.92 ± 0.32 | 5.28 ± 0.68 | 18.48 ± 1.58 | 6.16 ± 0.81 |
| CCL1 | 0.80 ± 0.1 | 0.80 ± 0.14 | 37.04 ± 2.94 | 0.60 ± 0.04† |
| CCL2 | 0.80 ± 0.95 | 0.76 ± 0.67 | 474.60 ± 49.46 | 0.80 ± 0.12† |
| CCL5 | 2.0 ± 0.4 | 1.9 ± 0.24 | 2305 ± 250.12 | 4.5 ± 0.6† |
| MIF | 337.08 ± 35.71 | 637.04 ± 52.47 | 1745.88 ± 153.5 | 918.04 ± 85.8† |
| Cytokines, AMPs, SOCS | ||||
| IL-6 | 5.92 ± .0.79 | 5.28 ± 0.48 | 17.40 ± 1.57 | 5.28 ± 0.65† |
| IL-20 | 1.00 ± 0.12 | 0.90 ± 0.10 | 0.98 ± 0.10 | 0.58 ± 0.04† |
| LL-37 | 1.00 ± 0.11 | 0.89 ± 0.09 | 0.85 ± 0.10 | 0.70 ± 0.08 |
| HBD2 | 1.00 ± 0.12 | 0.66 ± 0.08 | 1.11 ± 0.12 | 0.67 ± 0.08 |
| S100A7 | 1.00 ± 0.13 | 1.11 ± 0.2 | 2.61 ± 0.0.25 | 2.83 ± 0.3 |
| SOCS3 | 1.00 ± 0.12 | 1.13 ± 0.10 | 25.59 ± 2.65 | 2.14 ± 0.20† |
Note: IFN: interferon; TOF: tofacitinib; ICAM: intercellular adhesion molecule; HLA-DR: human leukocyte antigen-antigen D related; MHC: major histocompatibility complex; CXCL: CXC-chemokine ligand; CL: chemokine ligand; MIF: macrophage migration inhibitory factor; IL: interleukin; LL37: antimicrobial peptide; HBD: human-defensin; S100: S100 calcium-binding protein; SOCS: suppressor of cytokine signaling. ∗Keratinocyte cultures were left untreated or treated with 5 μM of tofacitinib and stimulated or not with 100 U/ml of IFN-γ. After 6 hours, IL-20, LL-37, HBD2, S100A7, and SOCS3 mRNA levels were analysed by real-time PCR and normalized to β-actin mRNA levels. Results are expressed as mean 2−ΔΔCT ± SD. After 24 hours, cells were stained with ICAM1, HLA-DR, and MHC-I mAb followed by FITC-conjugated anti-mouse IgG and then analysed by flow cytometry. Data are expressed as mean ΔMFI ± SD. At the same time, supernatants were collected and, chemokines and IL-6 were measured by Bioplex, except for CCL5 which has been evaluated by ELISA. Results are expressed as mean pg/ml ± SD. †p < 0.05 compared to untreated or stimulated keratinocytes.