TY - JOUR
T1 - Sera from patients with active systemic lupus erythematosus patients enhance the toll-like receptor 4 response in monocyte subsets
AU - Carvalheiro, Tiago
AU - Gomes, Diane
AU - Pinto, Ligia A
AU - Inês, Luis
AU - Lopes, Ana
AU - Henriques, Ana
AU - Pedreiro, Susana
AU - Martinho, António
AU - Trindade, Hélder
AU - Young, Howard A
AU - da Silva, José António Pereira
AU - Paiva, Artur
N1 - Publisher Copyright:
© 2015 Carvalheiro et al.
PY - 2015
Y1 - 2015
N2 - BACKGROUND: Systemic Lupus Erythematosus (SLE) is an auto-immune disease whose complex pathogenesis remains unraveled. Here we aim to explore the inflammatory ability of SLE patients' sera upon peripheral blood (PB) monocyte subsets and myeloid dendritic cells (mDCs) obtained from healthy donors.METHODS: In this study we included 11 SLE patients with active disease (ASLE), 11 with inactive disease (ISLE) and 10 healthy controls (HC). PB from healthy donors was stimulated with patients' sera, toll-like receptor (TLR) 4 ligand - lipopolysaccharide or both. The intracellular production of TNF-α was evaluated in classical, non-classical monocytes and mDCs, using flow cytometry. TNF-α mRNA expression was assessed in all these purified cells, after sera treatment.RESULTS: We found that sera of SLE patients did not change spontaneous TNF-α production by monocytes or dendritic cells. However, upon stimulation of TLR4, the presence of sera from ASLE patients, but not ISLE, significantly increased the intracellular expression of TNF-α in classical and non-classical monocytes. This ability was related to titers anti-double stranded DNA antibodies in the serum. High levels of anti-TNF-α in the patients' sera were associated with increased TNF-α expression by co-cultured mDCs. No relationship was found with the levels of a wide variety of other pro-inflammatory cytokines. A slight increase of TNF-α mRNA expression was observed in these purified cells when they were cultured only in the presence of SLE serum.CONCLUSIONS: Our data suggest that SLE sera induce an abnormal in vitro TLR4 response in classical and non-classical monocytes, reflected by a higher TNF-α intracellular expression. These effects may be operative in the pathogenesis of SLE.
AB - BACKGROUND: Systemic Lupus Erythematosus (SLE) is an auto-immune disease whose complex pathogenesis remains unraveled. Here we aim to explore the inflammatory ability of SLE patients' sera upon peripheral blood (PB) monocyte subsets and myeloid dendritic cells (mDCs) obtained from healthy donors.METHODS: In this study we included 11 SLE patients with active disease (ASLE), 11 with inactive disease (ISLE) and 10 healthy controls (HC). PB from healthy donors was stimulated with patients' sera, toll-like receptor (TLR) 4 ligand - lipopolysaccharide or both. The intracellular production of TNF-α was evaluated in classical, non-classical monocytes and mDCs, using flow cytometry. TNF-α mRNA expression was assessed in all these purified cells, after sera treatment.RESULTS: We found that sera of SLE patients did not change spontaneous TNF-α production by monocytes or dendritic cells. However, upon stimulation of TLR4, the presence of sera from ASLE patients, but not ISLE, significantly increased the intracellular expression of TNF-α in classical and non-classical monocytes. This ability was related to titers anti-double stranded DNA antibodies in the serum. High levels of anti-TNF-α in the patients' sera were associated with increased TNF-α expression by co-cultured mDCs. No relationship was found with the levels of a wide variety of other pro-inflammatory cytokines. A slight increase of TNF-α mRNA expression was observed in these purified cells when they were cultured only in the presence of SLE serum.CONCLUSIONS: Our data suggest that SLE sera induce an abnormal in vitro TLR4 response in classical and non-classical monocytes, reflected by a higher TNF-α intracellular expression. These effects may be operative in the pathogenesis of SLE.
KW - Classical monocytes
KW - Cytokines
KW - Myeloid dendritic cells
KW - Non-classical monocytes
KW - Serum
KW - Systemic lupus erythematosus
KW - Toll like receptor 4
UR - http://www.scopus.com/inward/record.url?scp=84930625609&partnerID=8YFLogxK
U2 - 10.1186/s12950-015-0083-2
DO - 10.1186/s12950-015-0083-2
M3 - Article
C2 - 26038677
SN - 1476-9255
VL - 12
SP - 38
JO - Journal of inflammation (London, England)
JF - Journal of inflammation (London, England)
IS - 1
M1 - 38
ER -