An essential update on the inventory of landslides triggered by the Jiuzhaigou Mw6.5 earthquake in China on 8 August 2017, with their spatial distribution analyses.

On August 8, 2017, a magnitude Mw6.5 (Ms7.0) earthquake occurred in Jiuzhaigou County, Aba Prefecture, in the northern part of Sichuan Province, China, with a focal depth of 20 km and an epicenter located at (33.2°N, 103.8°E). Due to the significant magnitude of the earthquake, a large number of coseismic landslides were triggered. Despite previous research conducted by experts on the landslides caused by the Jiuzhaigou earthquake, the actual number of landslides has been severely underestimated in the previously published papers. Through field surveys and visual interpretation of high-resolution remote sensing images before and after the mainshock, we have established a detailed inventory of earthquake-induced landslides. The results indicate that the event caused a minimum of 9428 landslides covering a total area of 18.82 km2. These landslides are mainly distributed in the IX intensity area of the earthquake. The landslides mainly consist of medium-sized landslides and debris flows. They predominantly occur in areas with an altitude ranging from 2600 m to 3600 m, with slopes greater than 30° and facing east and southeast. The Lower Carboniferous and Middle Carboniferous formations are more prone to triggering landslides, and landslides are more concentrated within 1 km of roads and in forested areas. Additionally, as the distance from roads and the epicenter increases, the values of LAP and LND decrease, indicating a positive correlation between the two. There are more landslides within 2 km from the fault and within a range of 6 km-9 km from the epicenter. In conclusion, this study provides a comprehensive landslide inventory with broader coverage and increased accuracy. It also conducts a comprehensive analysis of the spatial distribution patterns of landslides. This contributes to a deeper understanding of the causes of coseismic landslides and further research on the impact of landslides in affected areas.

FcγRIIb Exacerbates LPS-Induced Neuroinflammation by Binding with the Bridging Protein DAP12 and Promoting the Activation of PI3K/AKT Signaling Pathway in Microglia.

Introduction: This paper focuses on the expression and role of FcγRIIb in neuroinflammation, exploring the molecular mechanisms by which FcγRIIb interacts with the bridging protein DAP12 to regulate the PI3K-AKT signaling pathway that promote neuroinflammation and aggravate neuronal injury. Methods: LPS-induced neuroinflammation models in vivo and in vitro were constructed to explore the role and mechanism of FcγRIIb in CNS inflammation. Subsequently, FcγRIIb was knocked down or overexpressed to observe the activation of BV2 cell and the effect on PI3K-AKT pathway. Then the PI3K-AKT pathway was blocked to observe its effect on cell activation and FcγRIIb expression. We analyzed the interaction between FcγRIIb and DAP12 by Immunoprecipitation technique. Then FcγRIIb was overexpressed while knocking down DAP12 to observe its effect on PI3K-AKT pathway. Finally, BV2 cell culture supernatant was co-cultured with neuronal cell HT22 to observe its effect on neuronal apoptosis and cell activity. Results: In vivo and in vitro, we found that FcγRIIb expression was significantly increased and activated the PI3K-AKT pathway. Contrary to the results of overexpression of FcγRIIb, knockdown of FcγRIIb resulted in a significant low level of relevant inflammatory factors and suppressed the PI3K-AKT pathway. Furthermore, LPS stimulation induced an interaction between FcγRIIb and DAP12. Knockdown of DAP12 suppressed inflammation and activation of the PI3K-AKT pathway in BV2 cells, and meantime overexpression of FcγRIIb suppressed the level of FcγRIIb-induced AKT phosphorylation. Additionally, knockdown of FcγRIIb inhibited microglia activation, which induced neuronal apoptosis. Discussion: Altogether, our experiments indicate that FcγRIIb interacts with DAP12 to promote microglia activation by activating the PI3K-AKT pathway while leading to neuronal apoptosis and exacerbating brain tissue injury, which may provide a new target for the treatment of inflammatory diseases in the central nervous system.

Upregulation of CD226 on subsets of T cells and NK cells is associated with upregulated adhesion molecules and cytotoxic factors in patients with tuberculosis.

Human T cells and natural killer (NK) cells are major effector cells of innate immunity exerting potential immune surveillance against tuberculosis infection. CD226 is an activating receptor playing vital roles in the functions of T cells and NK cells during HIV infection and tumorigenesis. However, CD226 is a less-studied activating receptor during Mycobacterium tuberculosis (Mtb) infection. In this study, we used peripheral blood from tuberculosis patients and healthy donors to evaluate CD226 immunoregulation functions from two independent cohorts using Flow cytometry. Here, we found that a subset of T cells and NK cells that constitutively express CD226 exhibit a distinct phenotype in TB patients. In fact, the proportions of CD226+ and CD226- cell subsets differ between healthy people and tuberculosis patients, and the expression of immune checkpoint molecules (TIGIT, NKG2A) and adhesion molecules (CD2, CD11a) in CD226+ and CD226- subsets of T cells and NK cells exhibits special regulatory roles. Furthermore, CD226+ subsets produced more IFN-γ and CD107a than CD226- subsets in tuberculosis patients. Our results imply that CD226 may be a potential predictor of disease progression and clinical efficacy in tuberculosis by mediating the cytotoxic capacity of T cells and NK cells.

Development of the Social Media Engagement Scale for Adolescents.

This study aimed to develop the Social Media Engagement Scale for Adolescents (SMES-A), and evaluate its reliability and validity. The initial items were collected via open-ended questions, a literature review, and suggestions from psychological experts. A total valid sample of 2519 adolescents participated in this study. The results of the exploratory factor analysis (EFA) indicated that this scale was composed of three factors named affective engagement, behavioral engagement, and cognitive engagement, accounting for 56.01% of the total variance. The confirmatory factor analysis (CFA) confirmed the three-factor model. The affective engagement, behavioral engagement, and cognitive engagement were positively correlated with the criterion variables of objective social media use. The mean intra-correlation coefficients of the three factors were 0.523, 0.451, and 0.512. The Cronbach's alpha coefficients of the affective engagement, behavioral engagement, and cognitive engagement were from 0.709 to 0.804. Their McDonald's omega were 0.805, 0.805, and 0.712, which showed high reliability of this three-factor structure. The test-retest reliability of the three factors were all above 0.68 8 weeks later. Overall, our findings suggested that the SMES-A is a reliable and valid measurement to evaluate social media engagement among Chinese adolescents.

JNK/AP1 Pathway Regulates MYC Expression and BCR Signaling through Ig Enhancers in Burkitt Lymphoma Cells.

In Burkitt lymphoma (BL), a chromosomal translocation by which the MYC gene is fused to an immunoglobulin (Ig) gene locus is frequently found. The translocated MYC gene is overexpressed, which is the major driver of BL tumorigenesis. Studies have shown that Ig enhancers are essential for MYC overexpression, but the involved mechanisms are not fully understood. In addition, the survival of BL cells relies on B-cell receptor (BCR) signaling, which is determined by the levels of Ig molecules expressed on the cell surface. However, whether MYC has any impact on Ig expression and its functional relevance in BL has not been investigated. Herein, we show that MYC upregulates Ig kappa (Igκ) expression in BL cells through two Igκ enhancers, the intronic enhancer (Ei) and the 3' enhancer (E3'). Mechanistically, by activating the JNK pathway, MYC induces the phosphorylation of c-Fos/c-Jun and their recruitment to AP1 binding sites in the Igκ enhancers, leading to the activation of the enhancers and subsequent Igκ upregulation. The AP1-mediated activation of the Igκ enhancers is also required for the expression of the translocated MYC gene, indicating positive feedback for the MYC overexpression in BL cells. Importantly, interrupting the JNK pathway inhibits both Igκ and MYC gene expression and suppresses BL cell proliferation. Our study not only reveals a novel mechanism underlying MYC overexpression in BL but also suggests that targeting the JNK pathway may provide a unique strategy to suppress BL tumorigenesis.

Sleep disturbances in ankylosing spondylitis: a systematic review and meta-analysis.

The aim of this meta-analysis was to compare sleep outcomes of AS patients and controls. Six electronic databases were searched: PubMed, Embase, IndMed, Cochrane Library, CNKI and Web of Science. Statistical analyses were executed using Revman 5.3 software. Nine studies and a total of 3169 participants were included in the meta-analysis. When sleep was assessed using PSQI, significant differences were observed in subjective sleep quality, sleep latency, sleep efficiency, sleep disorders, sleep medication use and total PSQI between patients with AS and controls, and subjective sleep quality was most severely affected. In PSG, eight variables of sleep quality (stage I sleep, stage II sleep, slow wave sleep, rapid eye movement, arousal index, periodic leg movement index, sleep latency, sleep efficiency) were lower in AS patients than in controls. Three variables of sleep quality assessed by USI (estimated sleep time, sleep sufficiency index, number of awakenings per night) and two variables of sleep quality assessed by MOS sleep scale (sleep disturbance scale, sleep problem index II) were lower in AS patients than in controls. It indicated that AS patients experience more serious sleep disorders. Early recognition and appropriate interventions are essential to improve patients' sleep quality.

YY1 binds to the E3' enhancer and inhibits the expression of the immunoglobulin κ gene via epigenetic modifications.

The rearrangement and expression of immunoglobulin genes are regulated by enhancers and their binding transcriptional factors that activate or suppress the activities of the enhancers. The immunoglobulin κ (Igκ) gene locus has three important enhancers: the intrinsic enhancer (Ei), 3' enhancer (E3'), and distal enhancer (Ed). Ei and E3' are both required for Igκ gene rearrangement during early stages of B-cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3' and Ed. The transcription factor YY1 affects the expression of many genes involved in B-cell development, probably by mediating interactions between their enhancers and promoters. Herein, we found that YY1 binds to the E3' enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3' enhancer. Moreover, in germinal centre B cells and plasma cells, YY1 expression was reversely associated with Igκ levels, implying that YY1 might facilitate antibody affinity maturation in germinal centre B cells through the transient attenuation of Igκ expression.

Angiotensin II enhances the acetylation and release of HMGB1 in RAW264.7 macrophage.

The high-mobility group box-1 (HMGB1), as a highly conserved ubiquitous DNA-binding protein, has been widely studied in various diseases, including inflammation and tumor; however, fewer studies were focused on the mechanisms controlling HMGB1 release compared with the function of HMGB1. Previous studies have proven that ANG II can act as a pro-inflammatory cytokine, both of HMGB1 and ANG II were significantly upregulated in autoimmune diseases; however, the exact role of ANG II in regulating HMGB1 release have not been shown. The present study was to define the effects of ANG II on macrophages and the possible mechanisms in controlling HMGB1 release. Our results showed that ANG II can induce M1 macrophage polarization through upregulated the expression of HMGB1 and caused acetylation of HMGB1 and release via its dissociation from SIRT1, which in a positive feedback upregulates ANG II. Subsequently, HMGB1 inhibitors can reduce the ANG II-elicited polarize of macrophage. Meanwhile, we show that JAK/STAT pathways play an essential role in ANG II-induced HMGB1 nuclear translocation, JAK/STAT specific inhibitors can inhibit ANG II-induced HMGB1 expression. Taken together, our results provide a novel evidence that HMGB1 play a critical role in ANG II mediated macrophage polarization, and we suggest that ANG II mediated HMGB1 release via dissociation from SIRT1, induce hyperacetylation of HMGB1, thus for subsequent release, suggesting that the angiotensin II receptor antagonist is a potential drug target for inhibiting HMGB1 release in inflammation diseases.

Inhibition of microRNA-155 modulates endotoxin tolerance by upregulating suppressor of cytokine signaling 1 in microglia.

Endotoxin tolerance is an immunohomeostatic reaction to reiterant lipopolysaccharide (LPS) exposure that maintains a state of altered responsiveness in immune cells, resulting in the inhibition of the pro-inflammatory response and the resolution of inflammation. Microglia constitutes the first line of defense against endogenous and external challenges in the brain. MicroRNAs (miRs) serve a critical function in the regulation of inflammation. The aim of the present study was to investigate whether miR-155 regulates endotoxin tolerance. miR-155 and suppressor of cytokine signaling-1 (SOCS1) mRNA expression was measured using RT-qPCR. The expression of SOCS1 was measured by western blotting and immunofluorescence. TNF-α levels were detected by an enzyme-linked immunosorbent assay. The results indicated that miR-155 expression was significantly downregulated in the microglia and cortex tissue following the induction of endotoxin tolerance. This was consistent with an increase in the expression of SOCS1, a predicted target of miR-155 and key inhibitor of the inflammatory reaction. Transfection with miR-155 inhibitor significantly enhanced SOCS1 expression in the microglia following the induction of endotoxin tolerance. SOCS1 knockdown using short hairpin RNA partly inhibited the anti-inflammatory process and promoted the inflammatory response during endotoxin tolerance. The results of the current study indicate that miR-155 inhibition contributes to the development of endotoxin tolerance. Understanding how miRs regulate inflammatory mechanisms may facilitate the development of novel therapeutic strategies to treat CNS disorders.

Reg3ß from cardiomyocytes regulated macrophage migration, proliferation and functional skewing in experimental autoimmune myocarditis.

Macrophages play critical roles in inflammatory initiation, development, resolution and cardiac regeneration of myocarditis. However, Reg3ß, as a member of regenerating family of proteins, contributes to dedifferentiation of injury cardiomyocytes as well as cardiac function remodeling. It remains unclear whether Reg3ß was associated with macrophages reprogramming during autoimmune myocarditis. Our results showed that Reg3ß could effectively recruit macrophages, promoted their proliferation and phagocytosis, and facilitated their polarized into M2 macrophages. Macrophage, especially M1 phenotype contributed to Reg3ß production by cardiomyocytes. Our data also indicated that Reg3ß was involved in self-protection mechanism following cardiac injury or stress. This suggests that Reg3ß might be a critically protective factor of myocardium.

HMGB1 silencing in macrophages prevented their functional skewing and ameliorated EAM development: Nuclear HMGB1 may be a checkpoint molecule of macrophage reprogramming.

High-mobility group box 1 (HMGB1), an important inflammatory factor, plays significant roles in CD4+T cell differentiation, cancer and autoimmune disease development. Our previous data have demonstrated that HMGB1 contributes to macrophage reprogramming and is involved in experimental autoimmune myocarditis (EAM) development. In contrast to the well-explored function of HMGB1, little is known about the nuclear function. Whether HMGB1 can serve as an architectural factor and control functional skewing of macrophages remains unclear. Therefore, the present work was performed to address the above speculation. The adenovirus-mediated shRNA (Ad-shRNA) was employed to knock down HMGB1 in RAW264.7 and monocytes/macrophages of EAM mice. Our data showed that in vitro HMGB1 silencing limited functional skewing of macrophages and down-regulated inflammatory factors secretion, which can't be reversed by the exogenous HMGB1. In M1 polarization system, the phosphorylations of NF-κB, p38 and Erk1/2 were inhibited following HMGB1 silencing. In vivo, HMGB1 silencing could effectively ameliorate EAM development. Our data suggest that HMGB1 may be a checkpoint nuclear factor of macrophage reprogramming. Our findings also provide an exciting therapeutic method for inflammatory disorders.

Mycobacterium marinum Infection in Zebrafish and Microglia Imitates the Early Stage of Tuberculous Meningitis.

Mycobacterium tuberculosis (M. tuberculosis) invading and activating microglia causes the most serious subtypes of tuberculosis called tubercular meningitis. However, the developmental process of tubercular meningitis, especially the early phase, is poorly understood due to lacking well-established and well-accepted visible models in vitro and in vivo. Here, consistent with one recent report, we found Mycobacterium marinum (M. marinum) invade the zebrafish brain and subsequently cause granuloma-like structures. We further showed that M. marinum, which shares similar characteristics with M. tuberculosis, can invade microglia and replicate in microglia, which subsequently promote the secretion of pro-inflammatory cytokines such as IL-1ß, IL-6, and TNF-α. M. marinum infection in microglia can also promote autophagy, which conversely limits the replication of M. marinum. Thus, pharmacological activation of autophagy by rapamycin could prevent M. marinum replication. Our study provides in vivo and in vitro models to study underlying pathogenic mechanisms of tubercular meningitis by using M. marinum. Our results also showed that activation of autophagy could be a meaningful way to prevent tubercular meningitis.

ANG II facilitated CD11+ Ly6Chi cells reprogramming into M1-like macrophage through Erk1/2 or p38-Stat3 pathway and involved in EAM.

Macrophage, a highly plastic population, is widely distributed. Macrophage functions are settled and acquired polarization programs in response to microenvironmental signals and involved in many inflammatory disorders, such as experimental autoimmune myocarditis (EAM). Phenotypic and functional changes in macrophage are considered as an important determinant of disease progression and/or regression. Angiotensin II (ANG II), as a powerful proinflammatory factor, plays critical roles in inflammatory diseases and macrophage recruitment. It remains unclear whether ANG II contributed to the functional skewing of cardiac infiltrated monocytes/macrophage and involved in EAM development. Therefore, the present work was to address the above questions. Our data showed that ANG II contributed to CD11b+ Ly6Chi (CD11b+ Ly6G- Ly6C+ ) cells reprogramming into M1-like macrophage through Erk1/2 or p38/Stat3 pathway and the reprogramming M1-like cells promoted Th17 cells expansion; abrogation of ANG II-AT1 R axis significantly ameliorated cardiac injury. The present work first demonstrated a novel immune regulation role of ANG II; ANG II, as a powerful immune factor, promoted CD11b+ Ly6Chi inflammatory cells reprogramming into M1-like macrophage and involved in inflammatory disorders development; our results also indicated that ANG II may be a potential therapeutic target for inflammatory diseases.

JAK-STAT signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients.

Previous studies have revealed that bone marrow-mesenchymal stem cells (BM-MSCs) from systemic lupus erythematosus (SLE) patients exhibited early signs of senescence, which may participate in the development of SLE. However, the molecular mechanisms about this phenomenon have not been fully elucidated. In the current study, we aimed to investigate whether Janus kinase (JAK)-signaling transducers and activators of transcription (STAT) signaling mediated the senescence of BM-MSCs from SLE patients. Twelve female SLE patients and healthy subjects were enrolled in the study. All BM-MSCs were isolated by density gradient centrifugation. Western blot analysis was used to test the expression of JAK-STAT signaling molecules. We observed the activity of ß-gal of cells, the changes of cytoskeletal structure by F-actin staining, and the distribution of cell cycle by flow cytometry. BM-MSCs from SLE patients showed prominent features of senescence, and abnormal activation of JAK-STAT signaling transduction, high level of phosphorylated JAK2, and STAT3. After stimulation of IFN-γ in normal MSCs, JAK-STAT signaling was activated. The cell volume and the number of senescence-associated ß-galactosidase (SA-ß-gal) positive in SLE BM-MSCs were increased. The organization of cytoskeleton was nearly disordered. The rate of cell proliferation was decreased. AG490, the inhibitor of JAK2, and knockdown of STAT3 in BM-MSCs, could significantly reverse the senescence. In summary, our study indicated that JAK-STAT signaling pathway may play a critical role in the senescence of SLE BM-MSCs.

Lipopolysaccharide Preconditioning Induces an Anti-inflammatory Phenotype in BV2 Microglia.

Increasing evidence indicates that endotoxin tolerance is an essential immune-homeostatic response to repeated exposure to lipopolysaccharide (LPS) that induces a state of altered responsiveness in macrophage, resulting in repression of pro-inflammatory gene expression and increased expression of factors that mediate the resolution of inflammation. In this study, quantitative real-time polymerase chain reaction and Western blot for M1 and M2 markers were performed to characterize phenotypic changes of BV2 microglia. We found that the cytokine and chemokine expression during endotoxin tolerance were mostly similar to those found during M2 polarization. We further examined the expression of M1 and M2 markers in CD11b+ BV2 by double immunofluorescent staining. The expression of M2 markers (CD206) increased, whereas the expression of M1 (CD54) markers reduced during endotoxin tolerance. Moreover, expression of different transcription factor, known for their function in the regulation of pro- and anti-inflammatory reaction, was also different. Our data demonstrate that repeat LPS treatment activates a differentiation program that leads to microglial polarization toward M2-like phenotype.

Clinical and biological significance of HAX-1 overexpression in nasopharyngeal carcinoma.

HS1-associated protein X-1 (HAX-1) is an important marker in many types of cancers and contributes to cancer progression and metastasis. We examined the expression of HAX-1 in nasopharyngeal carcinoma (NPC) and experimentally manipulated its expression. We observed that HAX-1 expression is elevated in NPC and is correlated with lymph node metastasis, M classification, clinical stage, and poor prognosis. In addition, overexpression of HAX-1 promoted NPC proliferation both in vitro and in vivo. Exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. We found that NPC-derived exosomes are enriched in HAX-1 and accelerate NPC tumor growth and angiogenesis in vitro and in vivo. Furthermore, we demonstrated that oncogenic HAX-1 facilitates the growth of NPC when it is transferred via exosomes to recipient human umbilical vein endothelial cells (HUVECs). Oncogenic HAX-1 also increases the proliferation, migration, and angiogenic activity of HUVECs. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as HAX-1 to improve NPC treatment.

Macrophage-Microglia Networks Drive M1 Microglia Polarization After Mycobacterium Infection.

Central nervous system tuberculosis (CNS-TB) is caused by infection with Mycobacterium tuberculosis (Mtb). The inflammatory response following CNS-TB involves the activation of resident microglia and the infiltration of macrophages. However, it has not been clarified whether microglia can be polarized into the classically activated proinflammatory M1 phenotype or the alternatively activated anti-inflammatory M2 phenotype after Mtb infection. In this study, we found that BV2 treated with conditioned media from cultures of macrophages infected with Mycobacterium marinum (Mm) induced the expression of M1 phenotypic genes including iNOS, TNF-α, IL-1ß, IL-6, CCL2, and CXCL10 but reduced that of M2 phenotypic genes such as Arginase 1, Ym1, and CD163. These results suggest that polarization of microglia is partly mediated through macrophage-microglia interactions as a priming signal. Overall, these results provide new insights into the modulatory mechanisms of microglial polarization, thereby possibly facilitating the development of new therapies for CNS-TB infection via the regulation of microglial polarization through signalling derived from macrophages infected with mycobacteria.

Expression of SRC suppressed C kinase substrate in rat neural tissues during inflammation.

Src-suppressed C kinase substrate (SSeCKS), an in vivo and in vitro protein kinase C substrate, is a major lipopolysaccharide (LPS) response protein which markedly upregulated in several organs, including brain, lung, heart, kidney etc., indicating a possible role of SSeCKS in inflammatory process. However, the expression and biological function of SSeCKS during neuronal inflammation remains to be elucidated, so we established an inflammatory model injected with LPS to investigate the gene expression patterns of SSeCKS in neural tissues by using TaqMan quantitative real-time PCR and immunohistochemistry in rat. Real-time PCR showed that LPS stimulated the expression of SSeCKS mRNA in a dose- and time-dependent manner in sciatic nerves, spinal cords and dorsal root ganglions. Immunohistochemistry showed that SSeCKS colocalized with nerve fibers in sciatic nerve after LPS administration, but there was no colocalization between SSeCKS and Schwann cells. In addition, SSeCKS colocalized with neurons which existed in dorsal root ganglions and spinal cords. These findings indicated that SSeCKS might play some important roles in sciatic nerve fibers and neurons in spinal cords and dorsal root ganglions after LPS injection.

Mutated major histocompatibility complex class II transactivator up-regulates interleukin-33-dependent differentiation of Th2 subset through Nod2 binding for NLR (NOD-like receptor) signaling initiation.

Dominant-negative mutants of class II transactivator (mCIITAs) with N-terminal depletion have been used to repress the transcription of class II genes in xenotransplantation. Here, we report that mCIITA overexpressing myeloid cell line Ana-1 (Ana-1-mCIITA) derived from a C57BL/6 mouse was able to down-regulate the MHC class II expression and reverse immune responses from Th1 (IL-2(+)IFN-γ(+)STAT4(+)) to Th2 (IL-4(+)IL-5(+)IL-10(+)IL-13(+)STAT6(+)) when cocultured with T cells. Mechanism analysis indicated that the mCIITA protein is able to initiate a NOD-like receptor-related signaling pathway via binding of the cytoplasmic Nod2 protein, which was followed by activating RIP2, caspase 1, and IKK-α/ß. This ensures the expression of the genes encoding the cytokines IL-33, IL-1ß, and TNF-α; however, only the highly expressed IL-33 is responsible for inducing the type 2 response, with a skewed Th2 cytokine secretion (IL-4(+)IL-5(+)IL-10(+)IL-13(+)IL-2(-)IFN-γ(-)), which was completely prevented by the deactivation of the Nod2 gene with siRNA or by the blockage of the IL-33-related signaling using the mAb ST2L against the IL-33 receptor. mCIITA-mediated Th2 conversion was also successfully induced in vivo in a mCIITA-transgenic C57BL/6 mouse model. These results indicate that the Th1/Th2 balance could be regulated by an N terminus-depleted CIITA molecule via NOD-like receptor-related signaling, a property valuable for disease control, especially for inducing transplantation tolerance via the repression of class II expression and the attenuation of a Th1-dominant response.

TNF-α expression in Schwann cells is induced by LPS and NF-κB-dependent pathways.

Lipopolysaccharide (LPS) is recognized by Toll-like receptor 4 and activates mitogen-activated protein kinase, which leads to the induction of proinflammatory cytokine gene expression. In vivo, Schwann cells (SCs) at the site of injury may also produce tumor necrosis factor-α (TNF-α). However, the precise mechanism that regulates TNF-α synthesis is still not clear. The nuclear transcription factor-κB (NF-κB) is an important transcription factor which is involved in the regulation of host immune responses. In the present study, we found that LPS possessed a comparable specific activity for activation of NF-κB-dependent gene expression in SCs. We also observed IκB-α/IκB-ß degradation and the nuclear translocation of P65 due to LPS treatments. LPS-elicited TNF-α production in SCs was also drastically suppressed by SN50 (NF-κB inhibitor).