Chiral Primary Amine Catalyzed α-Arylation of Simple Ketones via Asymmetric Retro-Claisen Cleavage.

Highly enantioselective α-arylation of simple ketones has been achieved by chiral primary amine catalyzed asymmetric retro-Claisen cleavage of ß-diketones. This mild organocatalytic strategy enables the construction of α-aryl tertiary carbon stereocenters in good yields and excellent enantioselectivities (up to 98 % ee) with the para-quinone monoimines as aryl sources. Furthermore, oxidative catalytic asymmetric α-arylation has also been realized with free p-aminophenols.

Dynamic brain connectome and high risk of mental problem in clinical nurses.

With the growing population and rapid change in the social environment, nurses in China are suffering from high rates of stress; however, the neural mechanism underlying this occupation related stress is largely unknown. In this study, mental status was determined for 81 nurses and 61 controls using the Symptom Checklist 90 (SCL-90) scale. A subgroup (n = 57) was further scanned by resting-state functional MRI with two sessions. Based on the SCL-90 scale, "somatic complaints" and "diet/sleeping" exhibited the most prominent difference between nurses and controls. This mental health change in nurses was further supported by the spatial independent component analysis on functional MRI data. First, dynamic functional connectome analysis identified two discrete connectivity configurations (States I and II). Controls had more time in the State I than II, while the nurses had more time in the State II than I. Second, nurses showed a similar static network topology as controls, but altered dynamic properties. Third, the symptom-imaging correlation analysis suggested the functional alterations in nurses as potential imaging biomarkers indicating a high risk for "diet/sleeping" problems. In summary, this study emphasized the high risk of mental deficits in nurses and explored the underlying neural mechanism using dynamic brain connectome, which provided valuable information for future psychological intervention.

Characterization of autoantibodies and cytokines related to cutaneous lupus erythematosus.

OBJECTIVE: To investigate the profiles of anti-RPLP0, anti-galectin3 antibodies, interferon-α (IFN-α), interferon-λ1(IFN-λ1) and interleukin-17A/F(IL-17A/F) in the subtypes of cutaneous lupus erythematosus (CLE) including acute CLE (ACLE), subacute CLE (SCLE) and discoid lupus erythematosus (DLE). METHODS: Serum levels of autoantibodies and cytokines were determined by enzyme-linked immunoabsorbent assay (ELISA). Lupus lesions were evaluated by cutaneous lupus erythematosus disease area and severity index (CLASI). RESULTS: Serum anti-RPLP0, anti-galectin3 antibodies and IFN-λ1 were higher in systemic lupus erythematosus (SLE) patients with skin lesions than those without skin lesions, compared to healthy controls. IFN-α, IL-17A and IL-17F was elevated in all patients regardless of skin lesions. The two antibodies, IFN-α and IL-17A were positively correlated with the CLASI score in all patients with CLE. In addition, serum IL-17A was positively correlated to the CLASI score of ACLE, SCLE and DLE, while anti-RPLP0 and anti-galectin3 antibodies were only correlated to the score of SCLE and IL-17F to DLE. CONCLUSION: Serum anti-RPLP0, anti-galectin3 antibodies, IFN-α, IFN-λ1 and IL-17A/F are associated with the occurrence of lupus skin lesions regardless of the systemic complications, whereas the profiles of these inflammatory mediators vary with the subtypes of lupus skin lesions.

Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis.

Psoriasis-specific proteins dysregulated in keratinocytes and involved in the pathophysiological process of psoriasis remains elusive. We report here that epidermal galectin-3 expression is significantly downregulated in lesional skin, but not in non-lesional skin in psoriasis patients, nor in a group of diseases known as psoriasiform dermatitis clinically and histologically similar to psoriasis. The deficiency of epidermal galectin-3 is sufficient to promote development of psoriatic lesions, as evidenced by more severe skin inflammation in galectin-3 knockout (gal3-/-) mice, compared to wild-type mice, after imiquimod treatment, and in skin from gal3-/- mice grafted onto wildtype mice. The development of psoriatic-like lesions is attributable to 1) the spontaneously tuning up of psoriasis signatures in keratinocytes through JNK pathway; and 2) neutrophil accumulation caused by the enhanced leukocyte-recruiting capacity associated with overexpression of S100A7-9 and CXCL-1, 8 in keratinocytes with impaired galectin-3 expression. Psoriasis-like skin inflammation is significantly improved in gal-3-/- mice both by inhibition of neutrophils accumulation with a selective CXCR2 antagonist of SB225002, and by intracutaneous injection of recombinant galectin-3. Overall, these findings offer promising galectin-3-related diagnostic and therapeutic resolutions of psoriasis.

Galectin-3 Expression in Benign and Malignant Skin Diseases With Epidermal Hyperplasia.

Galectin-3 has been suggested relative to tumor genesis, progression, and metastasis in basal cell carcinoma and squamous cell carcinoma that are the most common skin cancers characterized by malignant epidermal proliferation. In this study, we evaluated galectin-3 expression in seborrheic keratosis, keratoacanthoma, and infectious diseases including verruca vulgaris, condyloma acuminatum, and chromoblastomycosis that are pathologically featured by benign epidermal proliferation. Galectin-3 expression was shown by immunohistochemical staining and quantified using the Image Pro Plus V6.0. We found that galectin-3 distributed evenly in normal skin around the body decreased significantly in all selected diseases compared with healthy controls, but it was comparable among each disease. These findings imply that galectin-3 do not differentiate between benign and malignant proliferation of keratinocytes.

Glycyrrhizin ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice and inhibits TNF-α-induced ICAM-1 expression via NF-κB/MAPK in HaCaT cells.

BACKGROUND/AIM: Glycyrrhizin (GL) is an important derivative of certain herbal medicines used in Asian countries. Currently, GL is used to treat hepatitis and allergic disease worldwide because of its anti-viral and anti-allergy effects. In addition to these prominent functions, GL likely regulates cellular functions such as tumor cell growth and cellular immunity. However, how GL affects the keratinocyte inflammation response remains poorly understood. The current paper investigates the effect of GL on psoriasis and explores the mechanisms involved. METHODS: We used an in vitro cell model of tumor necrosis factor (TNF)-α-induced keratinocyte inflammation and the topical application of imiquimod (IMQ) using an animal model (mouse skin) of IMQ-induced psoriasis-like inflammation (IPI) to investigate the effect of GL on skin inflammation. Cell viability was analyzed using the Cell Counting Kit-8 (CCK8). Carboxyfluorescein succinimidyl ester (CFSE) labeling was used to trace monocyte adherence to keratinocytes. A Western blot analysis was used to detect the expression of intercellular adhesion molecule 1 (ICAM-1) and the activation of the nuclear factor (NF)-κB/mitogen-activated protein kinase (MAPK) signaling pathway. A modified version of the Psoriasis Area Severity Index (PASI) was used to monitor disease severity. Hematoxylin and eosin (H&E) staining was used to observe pathological changes. An immunohistochemistry (IHC) analysis was used to detect ICAM-1 expression in mouse skin. RESULTS: GL treatment significantly reduced the levels of ICAM-1 in TNF-α-stimulated HaCaT cells, inhibited subsequent monocyte adhesion to keratinocytes, and suppressed the nuclear translation and phosphorylation of p65 following the degradation of inhibitor κB (IκB). GL treatment blocked the phosphorylation of extracellular signal-regulated kinase (ERK)/p38 MAPK. GL effectively delayed the onset of IPI in mice and ameliorated ongoing IPI, thereby reducing ICAM-1 expression in epidermal tissues. CONCLUSIONS: These results demonstrate that GL treatment ameliorates skin inflammation by inhibiting ICAM-1 expression via interference with the ERK/p38 MAPK and NF-κB signaling pathways in keratinocytes. Therefore, GL can be used as an anti-psoriasis drug.

Hydrogen sulfide inhibits abnormal proliferation of lymphocytes via AKT/GSK3ß signal pathway in systemic lupus erythematosus patients.

BACKGROUND/AIM: The abnormal activation of the AKT/GSK3ß signal pathway in lymphocytes from systemic lupus erythematosus (SLE) patients plays an important role in the pathogenesis of the disease. Recently Hydrogen sulfide (H2S) has been recognized as a crucial gaseous signaling molecule, involved in regulation of cell proliferation. However, the role of H2S in regulating the abnormal activation of lymphocytes from SLE patients has not been established. This study was conducted to investigate the effect of H2S on lymphocytes and to explore the mechanisms involved. METHODS: The lymphocytes were isolated from SLE patients with or without renal disease and healthy controls. The cells were treated as indicated in each experiment. Cell viability was analyzed by CCK-8. Cell cycle distribution was determined by flow cytometry. Western blot was used to detect the expression of phosphorylated AKT (ser473), GSK3ß (ser9) and CDK2, p27(Kip1) and p21(WAF1/CIP1). RESULTS: Our findings showed that proliferation of lymphocytes was stimulated following treatment with NaHS (a H2S donor) at low NaHS concentrations (<1mM) but inhibited at high NaHS concentrations (>2mM). Similar results were observed using GYY4137, which is a slow-releasing H2S donor. Pretreatment of lymphocytes from SLE patients with NaHS at high concentrations prior to exposure to phytohemagglutinin (PHA) significantly attenuated proliferation, evidenced by decrease in cell viability and S phase distribution of cell cycle. Pretreatment with NaHS decreased PHA-induced expression of CDK2, phosphorylation levels of AKT (ser473) and GSK3ß (ser9) and increased the expression of p27(Kip1) and p21(WAF1/CIP1). Moreover, pretreatment with NaHS blunted the stimulation of SLE lymphocyte proliferation by GSK3ß inhibitor lithium chloride. CONCLUSION: These results demonstrate that H2S inhibits the abnormal activation of lymphocytes from SLE patients throuqh the AKT/GSK3ß signal pathway.

Mesenchymal stem cell transplantation inhibits abnormal activation of Akt/GSK3ß signaling pathway in T cells from systemic lupus erythematosus mice.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by activation and proliferation of autoreactive T cells and B cells. We examined changes in cell cycle progression of T cells from MRL/lpr mice with or without allogenic bone marrow mesenchymal stem cells (BMMSCs) treatment and analyzed the expression of cell cycle associated proteins. In addition, the Akt/GSK3ß protein kinase cascade was studied. We demonstrated that high-dose MSCs transplantation effectively ameliorated disease activity in MRL/lpr mice. BMMSCs treatment inhibited G1/S transition of the abnormal lupus T lymphocytes. Moreover, it increased the expression of p21(WAF1/CIP1) and p27(Kip1) and decreased the expression of CDK2. Furthermore, high-dose MSCs inhibited abnormal activation of the Akt/GSK3ß signaling pathway of T cells from MRL/lpr mice. Our results suggest that high-dose BMMSCs transplantation successfully treated MRL/lpr lupus mice by inhibiting abnormal activation of Akt/GSK3ß signaling pathway of T cells.

Highly Stereoselective Construction of ß,ß-Diaryl-α-Branched Ketones by the Chiral Primary Amine-Catalyzed Asymmetric Retro-Claisen Reaction.

Highly diastereo- and enantioselective retro-Claisen reaction of ß-diketones with o-quinone methides has been developed by chiral primary amine catalysis. This reaction allows for efficient synthesis of chiral ß,ß-diaryl-α-branched ketones in moderate to good yields with excellent stereoselectivities. The reaction occurs via a tandem sequence of benzylic C-C bond formation, C-C bond cleavage, and stereospecific enamine protonation. This strategy uses o-quinone methides as diaryl precursors and features a broad substrate scope, mild conditions, and a high degree of stereocontrol.

Biochemical characterization of UDP-Gal:GlcNAc-pyrophosphate-lipid ß-1,4-Galactosyltransferase WfeD, a new enzyme from Shigella boydii type 14 that catalyzes the second step in O-antigen repeating-unit synthesis.

The O antigen is the outer part of the lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria and contains many repeats of an oligosaccharide unit. It contributes to antigenic variability and is essential to the full function and virulence of bacteria. Shigella is a Gram-negative human pathogen that causes diarrhea in humans. The O antigen of Shigella boydii type 14 consists of repeating oligosaccharide units with the structure [→6-d-Galpα1→4-d-GlcpAß1→6-d-Galpß1→4-d-Galpß1→4-d-GlcpNAcß1→]n. The wfeD gene in the O-antigen gene cluster of Shigella boydii type 14 was proposed to encode a galactosyltransferase (GalT) involved in O-antigen synthesis. We confirmed here that the wfeD gene product is a ß4-GalT that synthesizes the Galß1-4GlcNAcα-R linkage. WfeD was expressed in Escherichia coli, and the activity was characterized by using UDP-[³H]Gal as the donor substrate as well as the synthetic acceptor substrate GlcNAcα-pyrophosphate-(CH2)11-O-phenyl. The enzyme product was analyzed by liquid chromatography-mass spectrometry (LC-MS), high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and galactosidase digestion. The enzyme was shown to be specific for the UDP-Gal donor substrate and required pyrophosphate in the acceptor substrate. Divalent metal ions such as Mn²(+), Ni²(+), and, surprisingly, also Pb²(+) enhanced the enzyme activity. Mutational analysis showed that the Glu101 residue within a DxD motif is essential for activity, possibly by forming the catalytic nucleophile. The Lys211 residue was also shown to be required for activity and may be involved in the binding of the negatively charged acceptor substrate. Our study revealed that the ß4-GalT WfeD is a novel enzyme that has virtually no sequence similarity to mammalian ß4-GalT, although it catalyzes a similar reaction.

Biosynthesis of UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose by WekG, WekE, WekF, and WekD: Enzymes in the Wek pathway responsible for O-antigen Assembly in Escherichia coli O119.

Considering the importance of bacterial glycoconjugates on virulence and host mimicry, there is a need to better understand the biosynthetic pathways of these unusual sugars to identify critical targets involved in bacterial pathogenesis. In this report, we describe the cloning, overexpression, purification, and biochemical characterization of the four central enzymes in the biosynthesis pathway for UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose, WekG, WekE, WekF, and WekD. Product peaks from enzyme-substrate reactions were detected by using a combination of capillary electrophoresis (CE) and electrospray ionization-mass spectrometry (ESI-MS). Putative enzyme assignments were provided by protein sequence analysis. Combined with the mass spectrometric characterization of pathway intermediates, we propose a biosynthetic pathway for UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose. This process involves C-4, C-6 dehydration, C-4 amination, and formylation. CID-ESI-MSn result confirmed that the final product is a 4 formamido derivative too rather than the 3 formamido derivatives as reported earlier.

Identification of three new compounds that directly target human serine hydroxymethyltransferase 2.

Mitochondrial serine hydroxymethyltransferase 2 (SHMT2) is an important drug target in the one-carbon metabolic pathway, since its activity is critical for purine and pyrimidine biosynthesis. Additionally, it plays a prominent role during metabolic reprogramming of cancer cells, and SHMT2 inhibitors have proven useful as anticancer drugs. Compared to drugs targeting one-carbon metabolic enzymes (mainly dihydrofolate reductase and thymidylate synthase) that have been used for clinical treatment of cancer, efficient SHMT2-specific inhibitors are lacking. Therefore, we established a direct system for virtual screening, protein expression, and identification of inhibitors targeting SHMT2. First, 27 compounds qualifying as potential SHMT2 inhibitors were selected for biological activity verification through virtual screening of the 210 thousand compounds registered in the Specs database. Second, these 27 hits were subjected to quick screening by an in vitro non-competitive kinetic assay of SHMT2 single-enzyme catalysis. This allowed us to identify three compounds featuring medium-strength and non-competitive inhibition of SHMT2: AM-807/42004511 (IC50  = 14.52 ± 4.1665 µM), AM-807/40675298 (IC50  = 12.74 ± 5.8991 µM), and AM-807/42004633 (IC50  = 9.43 ± 0.5646 µM). We describe a quick screening method for the identification of inhibitors targeting SHMT2, providing a basis for subsequent identification and screening of new inhibitors.

Structure of the O-antigen of Salmonella O66 and the genetic basis for similarity and differences between the closely related O-antigens of Escherichia coli O166 and Salmonella O66.

O-antigen is a component of the outer membrane of Gram-negative bacteria and is one of the most variable cell surface constituents, leading to major antigenic variability. The O-antigen forms the basis for bacterial serotyping. In this study, the O-antigen structure of Salmonella O66 was established, which differs from the known O-antigen structure of Escherichia coli O166 only in one linkage (most likely the linkage between the O-units) and O-acetylation. The O-antigen gene clusters of Salmonella O66 and E. coli O166 were found to have similar organizations, the only exception being that in Salmonella O66, the wzy gene is replaced by a non-coding region. The function of the wzy gene in E. coli O166 was confirmed by the construction and analysis of deletion and trans-complementation mutants. It is proposed that a functional wzy gene located outside the O-antigen gene cluster is involved in Salmonella O66 O-antigen biosynthesis, as has been reported previously in Salmonella serogroups A, B and D1. The sequence identity for the corresponding genes between the O-antigen gene clusters of Salmonella O66 and E. coli O166 ranges from 64 to 70 %, indicating that they may originate from a common ancestor. It is likely that after the species divergence, Salmonella O66 got its specific O-antigen form by inactivation of the wzy gene located in the O-antigen gene cluster and acquisition of two new genes (a wzy gene and a prophage gene for O-acetyl modification) both residing outside the O-antigen gene cluster.

The diagnostic benefit of antibodies against ribosomal proteins in systemic lupus erythematosus.

BACKGROUND: Anti-ribosomal P (anti-Rib-P) antibody is a specific serological marker for systemic lupus erythematosus (SLE) and routinely tested by targeting the common epitope of three ribosomal proteins of P0, P1 and P2. This study aimed to investigate if testing antibodies against individual ribosomal protein, but not the common epitope, is required to achieve the best diagnostic benefit in SLE. METHODS: The study included 82 patients with SLE and 22 healthy donors. Serum antibodies were determined by ELISA and immunoblot. RESULTS: The prevalence of each antibody determined by ELISA was 35.4% (anti-Rib-P), 45.1% (anti-Rib-P0), 32.9% (anti-Rib-P1) and 40.2% (anti-Rib-P2) at 99% specificity, respectively. Of 53 patients with negative anti-Rib-P antibody, 21 (39.6%) were positive for anti-Rib-P0, 9 (17.0%) for anti-Rib-P1 and 12 (22.6%) for anti-Rib-P2 antibody. The positive rate of anti-Rib-P antibody detected by ELISA was close to the results by immunoblot (33.4%). Patients with any of these antibodies were featured by higher disease activity and prevalence of skin rashes than those with negative antibodies. Moreover, each antibody was particularly related to some clinical and laboratory disorders. The distribution of subclasses of IgG1-4 was varied with each antibody. Anti-Rib-P0 IgG1 and IgG3 were strongly correlated with disease activity and lower serum complement components 3 and 4. CONCLUSIONS: Anti-Rib-P antibody is not adequate to predict the existence of antibodies against ribosomal P0, P1 and P2 protein. The examination of antibodies against each ribosomal protein is required to achieve additional diagnostic benefit and to evaluate the association with clinical and serological disorders as well.

Asymmetric Retro-Claisen Reaction by Synergistic Chiral Primary Amine/Palladium Catalysis.

We described herein a chiral primary amine/palladium catalyzed asymmetric retro-Claisen reaction of ß-diketones with salicylic carbonates. A series of chiral α-alkylated ketones and macrolides were obtained with good yields and excellent enantioselectivities upon a sequence of decarboxylative benzylation, retro-Claisen cleavage, and enamine protonation. This strategy features broad substrate scope, mild conditions, as well as high atom economy with salicylic carbonates as the o-quinone methide precursors.

Aromatic Aminocatalysis.

Aromatic aminocatalysis refers to transformations that employ aromatic amines, such as anilines or aminopyridines, as catalysts. Owing to the conjugation of the amine moiety with the aromatic ring, aromatic amines demonstrate distinctive features in aminocatalysis compared with their aliphatic counterparts. For example, aromatic aminocatalysis typically proceeds with slower turnover, but is more active and conformationally rigid as a result of the stabilized aromatic imine or iminium species. In fact, the advent of aromatic aminocatalysis can be traced back to before the renaissance of organocatalysis in the early 2000s. So far, aromatic aminocatalysis has been widely applied in bioconjugation reactions through transamination; in asymmetric organocatalysis through imine/enamine tautomerization; and in cooperative catalysis with transition metals through C-H/C-C activation and functionalization. This Focus Review summarizes the advent of and major advances in the use of aromatic aminocatalysis in bioconjugation reactions and organic synthesis.

Identification of Mutation Regions on NF1 Responsible for High- and Low-Risk Development of Optic Pathway Glioma in Neurofibromatosis Type I.

Neurofibromatosis type I is a rare neurocutaneous syndrome resulting from loss-of-function mutations of NF1. The present study sought to determine a correlation between mutation regions on NF1 and the risk of developing optic pathway glioma (OPG) in patients with neurofibromatosis type I. A total of 215 patients with neurofibromatosis type I, from our clinic or previously reported literature, were included in the study after applying strict inclusion and exclusion criteria. Of these, 100 patients with OPG were classified into the OPG group and 115 patients without OPG (aged ≥ 10 years) were assigned to the Non-OPG group. Correlation between different mutation regions and risk of OPG was analyzed. The mutation clustering in the 5' tertile of NF1 was not significantly different between OPG and Non-OPG groups (P = 0.131). Interestingly, patients with mutations in the cysteine/serine-rich domain of NF1 had a higher risk of developing OPG than patients with mutations in other regions [P = 0.019, adjusted odds ratio (OR) = 2.587, 95% confidence interval (CI) = 1.167-5.736], whereas those in the HEAT-like repeat region had a lower risk (P = 0.036, adjusted OR = 0.396, 95% CI = 0.166-0.942). This study confirms a new correlation between NF1 genotype and OPG phenotype in patients with neurofibromatosis type I, and provides novel insights into molecular functions of neurofibromin.

Increased serum IL-36α and IL-36γ levels in patients with systemic lupus erythematosus: Association with disease activity and arthritis.

IL-36 cytokines (IL-36Ra, IL-36α, IL-36ß and IL-36γ) belong to the IL-1 family and have been linked to several autoimmune diseases. However, little is known about the relationships between systemic lupus erythematosus (SLE) and IL-36 cytokines. In this study, serum IL-36 cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA), and their associations with SLE-related parameters were analyzed in 72 SLE patients and 63 healthy controls. Additionally, IL-36 cytokine mRNA levels were assessed in 30 of 72 SLE patients and 20 of 63 healthy controls using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Compared to healthy controls, SLE patients had significantly decreased serum IL-36Ra levels (P = 0.001) and markedly increased serum IL-36α and IL-36γ levels (P = 0.004 and P = 0.001, respectively). Serum IL-36α and IL-36γ levels were significantly higher in active SLE patients [SLE Disease Activity Index (SLEDAI) score ≥ 5] than in inactive patients (SLEDAI score ≤ 4) (P = 0.020 and P = 0.017, respectively). Serum IL-36α and IL-36γ levels were strongly correlated with SLEDAI score (r = 0.308, P = 0.008 and r = 0.400, P = 0.001, respectively) and complement C3 levels (r = -0.276, P = 0.019 and r = -0.314, P = 0.007, respectively). Moreover, SLE patients with arthritis had significantly higher serum IL-36α and IL-36γ levels than those without arthritis (P = 0.001 and P < 0.001, respectively). Our study indicates that the imbalanced antagonist/agonist profile of IL-36 cytokines may be linked to SLE pathogenesis. Furthermore, IL-36α and IL-36γ may participate in arthritis and may be good biomarkers of SLE disease activity.

Pathogenesis of cutaneous lupus erythema associated with and without systemic lupus erythema.

Cutaneous lupus erythematosus (CLE) can be an individual disease only involving skin, or presents as part of the manifestations of SLE. A small proportion of CLE may progress into SLE, however, the underlying pathogenic mediators remain elusive. By only including researches that clearly described if the subtypes of CLE presented by enrolled subjects was associated with or without SLE, we provided an overview of antibodies, inflammatory cells and inflammatory molecular mediators identified in blood and skin that were possibly involved in lupus skin damages. IgG autoantibodies are crucial for the development of CLE associated with SLE, but the circulating inflammatory cells and molecular mediators require further studies to provide definitive proof for their association with skin damages. Discoid lupus erythematosus (DLE) is the most common subtype of CLE. For DLE without associated with SLE (CDLE), it is lack of evidences if autoantibodies and circulating inflammatory cells are involved in the pathogenesis or not, but is clear that the cutaneous inflammatory infiltrates are dominated by Th1, but not Th17 cells in contrast to the various complex profile in SLE. As the major target cells in skin, keratinocytes may participate the pathophysiological process by increase cell apoptosis and the production of proinflammatory cytokines in SLE and CDLE. Insights into the similarities and differences of the pathogenesis of CLE and CLE associated with SLE will also improve our therapeutic strategies for CLE that is currently adopted from SLE, and prevent the progression of CLE to SLE by providing interventions within an appropriate window of disease development.