Selective Immunomodulation of Inflammatory Pathways in Keratinocytes by the Janus Kinase (JAK) Inhibitor Tofacitinib: Implications for the Employment of JAK-Targeting Drugs in Psoriasis

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. compared to untreated or stimulated keratinocytes.