Immunization with Tp0954, an adhesin of Treponema pallidum, provides protective efficacy in the rabbit model of experimental syphilis.

Syphilis, a chronic multisystemic disease caused by spirochete Treponema pallidum subspecies pallidum infection, continues to be a serious global health problem and congenital syphilis remains a major cause of adverse outcomes in pregnancy in developing countries. The development of an effective vaccine is the most cost-effective way to eliminate syphilis, but so far has been elusive. Here, we evaluated the immunogenicity and protective efficacy of Tp0954, a T. pallidum placental adhesin, as a potential vaccine candidate in a New Zealand White rabbit model of experimental syphilis. Animals immunized with recombinant Tp0954 (rTp0954) produced high titers of Tp0954-specific serum IgG, high levels of IFN-γ from splenocytes and specific splenocyte proliferation response when compared to control animals immunized with PBS and Freund's adjuvant (FA). Furthermore, rTp0954 immunization significantly delayed the development of cutaneous lesions, promoted inflammatory cellular infiltration at the primary lesion sites, as well as inhibited T. pallidum dissemination to distal tissues or organs when compared with that of the control animals. In addition, the naïve rabbits receiving popliteal lymph nodes from Tp0954-immunized, T. pallidum-challenged animals were not infected by T. pallidum, confirming sterile immunity. These findings suggest that Tp0954 is a potential vaccine candidate against syphilis.

A randomized, single-blind, multi-center clinical observational study of a new super lubricath coating catheter latex catheters using in urethral catheterization.

Polymer polyvinylpyrrolidone (PVP) can be described as the main coating. After heating and curing, it is able to build a strong adhesion to the latex catheter for creating a durable and effective hydrophilic coating. In this study, we aim to explore the advantages and disadvantages of the new super lubricath latex catheter PVP coating compared with the common latex catheter. 148 patients who participated in the study were completely randomly divided into two groups, the observation group and the control group. When the urinary catheter was incubated, indwelling in subjects' body, and removed from the subjects, the researchers accordingly recorded the subjects' comfort feedback, device safety evaluation and the patient's vital signs, relevant blood and urine examination index, electrocardiogram (ECG) changes and recorded various adverse events. PVP super lubricath coating latex catheter offered better comfort, less damage to the urethra, and no significant disadvantage in safety compared to regular latex catheters, improving quality of care and patient satisfaction compared to regular latex urinary catheters.

Treponema pallidum FlaA2 inducing the release of pro-inflammatory cytokines is mediated via TLR2 in keratinocytes.

BACKGROUND: Syphilis, caused by Treponema pallidum (T. pallidum), is a multi-organ, multiple systems, multi-stage sexually transmitted diseases with various clinical manifestations, among of which pathological lesions of skin and mucosa are the typical clinical manifestations of syphilis. However, the immunopathogenesis of this process is poorly understood. T. pallidum flagellin FlaA2, as a part of the important organelle responsible for the causative agent's motility, may contributes to the host skin inflammatory response. OBJECTIVES: To determine the mechanisms of T. pallidum FlaA2 stimulating the expression of pro-inflammatory cytokines in human keratinocytes. METHODS: Recombinant FlaA2 protein was performed to stimulate human keratinocytes. The mRNA transcription levels and protein expression levels of IL-6 and IL-8 were detected by qRT-PCR and ELISA, respectively. Western blot was used to detect the total protein and phosphorylation levels of ERK, p38, JNK and NF-κB, respectively. The intracellular location of NF-κB p65 was detected by immunofluorescence staining. RESULTS: Recombinant FlaA2 could considerably induced the expression of pro-inflammation cytokines IL-6 and IL-8 in HaCaT cells, and FlaA2-induced IL-6 and IL-8 secretion could be decreased by inhibiting TLR2 using pZERO-hTLR2. Further investigation showed that FlaA2 could activate the phosphorylation of ERK, p38 and IκBα and FlaA2-stimulated secretion of IL-6, IL-8 were attenuated by ERK, p38 and NF-κB inhibitors in HaCaT cells. Moreover, FlaA2 activates the ERK, p38 and NF-κB pathways through TLR2 signaling pathway in HaCaT cells. CONCLUSIONS: From the findings above, these results confirm that T. pallidum FlaA2 activates ERK, p38 and NF-κB signaling pathway through TLR2 pathway to induce the production of IL-6 and IL-8, which could contribute to enhance the understanding of the skin inflammatory response induced by the pathogen in syphilis patients.

Assessment of recombinant antigens Tp0100 and Tp1016 of Treponema pallidum for serological diagnosis of syphilis.

OBJECTIVE: To discover novel serodiagnostic candidates for the serological diagnosis of syphilis. METHODS: Two recombinant Treponema pallidum proteins Tp0100 and Tp1016 were expressed, purified, and identified by Western Blotting. A total of 600 clinical serum samples were tested with the Tp0100-based ELISA, the Tp1016-based ELISA, and the commercial LICA Syphilis TP kit (ChIVD, Beijing, China). The sensitivities were determined by testing 340 samples from individuals with clinically diagnosed primary, secondary, latent, and tertiary syphilis. The specificities were determined by screening 260 samples from healthy controls and individuals with potentially cross-reactive infections, including leptospirosis, Lyme disease, hepatitis B, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus. Kappa (κ) values were applied to compare the agreement between clinical syphilis diagnosis and the Tp0100-based ELISA, the Tp1016-based ELISA, or the LICA Syphilis TP test. RESULTS: Using clinical syphilis diagnosis as the gold standard, Tp0100 exhibited an overall sensitivity of 95.6% and specificity of 98.1% for testing IgG antibody while Tp1016 demonstrated only an overall sensitivity of 75.0% and specificity of 79.6%. In contrast, the LICA Syphilis TP test revealed an overall sensitivity of 97.6% and specificity of 96.2%. In addition, the overall percent agreement and corresponding κ values were 96.7% (95% CI 95.6%-97.8%) and 0.93 for the Tp0100-based ELISA, 77.0% (95% CI 74.3%-79.7%) and 0.54 for the Tp1016-based ELISA, and 97.0% (95% CI 96.0%-98.0%) and 0.94 for the LICA Syphilis TP test, respectively. CONCLUSION: The recombinant T. pallidum protein Tp0100 shows promise as a novel diagnostic antigen in the serological tests for syphilis.

The Role of miR-129-5p in Cancer: A Novel Therapeutic Target.

miRNA-129-5p belongs to the microRNA-129 (miRNA-129) family. miRNA-129-5p is expressed in many tissues and organs of the human body, and it regulates a wide range of biological functions. The abnormal expression of miRNA-129-5p is related to the occurrence and development of a variety of malignant tumors. miRNA-129-5p plays an important role in the tumorigenesis process and functions by promoting or inhibiting tumors. However, the role of miRNA-129-5p in cancer remains controversial. This article reviews the different biological functions of miRNA- 129-5p in cancer and provides ideas for research in this field to guide the development of targeted therapies and drugs for malignant tumors.

lncRNAs as Hallmarks for Individualized Treatment of Gastric Cancer.

Gastric cancer is a global cancer with a high mortality rate. A growing number of studies have found the abnormal expression of lncRNA (long noncoding RNA) in many tumors, which plays a role in promoting or inhibiting cancer. Similarly, lncRNA abnormal expression plays an essential biological function in gastric cancer. This article focuses on lncRNA involvement in the development of gastric cancer in terms of cell cycle disorder, apoptosis inhibition, metabolic remodeling, promotion of tumor inflammation, immune escape, induction of angiogenesis, and Epithelial Mesenchymal Transition (EMT). The involvement of lncRNA in the development of gastric cancer is related to drug resistance, such as cisplatin and multi-drug resistance. It can also be used as a potential marker for the diagnosis and prognosis of gastric cancer and a target for the treatment. With an in-depth understanding of the mechanism of lncRNA in gastric cancer, new ideas for personalized treatment of gastric cancer are expected.

Two Potential Syphilis Vaccine Candidates Inhibit Dissemination of Treponema pallidum.

Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a major public health problem worldwide. Recent increases in the number of syphilis cases, in addition to the lack of an efficient vaccine against T. pallidum for humans, highlights an urgent need for the design and development of an efficacious syphilis vaccine. Here, we assess the vaccine potential of the adhesion protein Tp0136 and the outer membrane protein Tp0663. Rabbits were subcutaneously immunized with recombinant proteins Tp0136, Tp0663, or control PBS. Immunization with Tp0136 or Tp0663 generated a strong humoral immune response with high titers of IgG, as assessed by ELISA. Moreover, animals immunized with Tp0136 or Tp0663 exhibited attenuated lesion development, increased cellular infiltration at the lesion sites, and inhibition of treponemal dissemination to distant organs compared to the unimmunized animals. These findings indicate that Tp0136 and Tp0663 are promising syphilis vaccine candidates. Furthermore, these results provide novel and important information for not only understanding the pathogenic mechanisms of spirochetes, but also the development of spirochete-specific subunit vaccines.

Identification of key genes and pathways in syphilis combined with diabetes: a bioinformatics study.

We noticed that syphilis patients seem to be more susceptible to diabetes and the lesions often involve the kidneys, but the pathogenesis is not yet completely understood. In this study, microarray analysis was performed to investigate the dysregulated expressed genes (DEGs) in rabbit model of syphilis combined with diabetes. A total of 1045 genes were identified to be significantly differentially expressed, among which 571 were up-regulated and 474 were down-regulated (≥ 2.0fold, p < 0.05). Using the database visualization and integration discovery for the Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis. The downregulated DEGs were significantly enriched for biosynthesis of antibiotics, carbon metabolism and protein digestion, while the upregulated DEGs were mainly enriched for cancer and PI3K-Akt signaling pathway. Molecular Complex Detection (MCODE) plugins were used to visualize protein-protein interaction (PPI) network of DEGs and Screening for hub genes and gene modules. ALB, FN1, CASP3, MMP9, IL8, CTGF, STAT3, IGF1, VCAM-1 and HGF were filtrated as the hub genes according to the degree of connectivity from the PPI network. To the best of our knowledge, this study is the first to comprehensively identify the expression patterns of dysregulated genes in syphilis combined with diabetes, providing a basis for revealing the underlying pathogenesis of syphilis combined with diabetes and exploring the goals of therapeutic intervention.

A comparison of genotyping tool in Treponema pallidum: Review and meta-analysis.

BACKGROUND: To decipher the molecular epidemiology of the Treponema pallidum subspecies, pallidum, researchers have developed different molecular typing schemes which identify strains type from clinical specimens. However, the results of these studies show remarkable diversity. METHODS: We searched for literature in PubMed, MEDLINE, Web of Sciences, and OVID from January 1998 to January 2019, in order to compare the efficiency of typing schemes using published evidence for systematic reviews and meta-analyses. RESULTS: From the 43 studies included, the overall typing efficiency of Treponema pallidum was 71.4% (95% CI: 63.2-78.9%). Subgroup analyses indicated that the typing efficiency of CDC-typing (CDCT, 68.2%, 95% CI: 53.6-81.2%) was worse than those of enhanced CDC-typing (ECDCT, 72.3%, 95% CI: 60-83.1%), CDC-rspA (81.6%, 95% CI: 76.1-86.6%), multi-locus sequence typing (MLST, 67.1%, 95% CI: 61.1-72.7), and sequencing-based molecular typing (SBMT, 71.6%, 95% CI: 50-89.2%). A limitation of this review is that the studies included employed different criteria to collect and investigate samples of Treponema pallidum, which could contribute to heterogeneity. CONCLUSIONS: This analysis suggests that CDCT is an inferior scheme in molecular typing, the discriminatory power was very similar for ECDCT and SBMT. Other factors contributing to the heterogeneity between typing studies warrants further study.

The N-terminal D1 domain of Treponema pallidum flagellin binding to TLR5 is required but not sufficient in activation of TLR5.

Syphilis is a chronic bacterial infection caused by Treponema pallidum (T pallidum) and the pathogenesis that T pallidum infection induces immunopathological damages in skin and other tissues remains unclear. We have previously reported that recombinant flagellins of T pallidum can elicit IL-6 and IL-8 transcriptions via TLR5 pathway. To identify the domains which induced the pro-inflammatory activity and the importance of the interactions between TLR5 and domains, homology-based modelling and comparative structural analyses revealed that Tpflagellins can combine with TLR5 directly. Deletion mutations showed that the ND1 domain binding to TLR5 is required but not sufficient in TLR5 activation. Moreover, site-directed mutagenesis analysis indicated that the arginine residue (Tpflagellins R89) of the ND1 domain and its adjacent residues (Tpflagellins L93 and E113) constitute a hot spot that elicits IL-6, IL-8 transcriptions and TLR5 activation, and affects the binding of Tpflagellins to TLR5. Taken together, these results give insight into the pathogenesis of T pallidum and may contribute to the future design of Tpflagellins-based therapeutics and syphilis vaccine.

BCL10 in cell survival after DNA damage.

The complex defense mechanism of the DNA damage response (DDR) developed by cells during long-term evolution is an important mechanism for maintaining the stability of the genome. Defects in the DDR pathway can lead to the occurrence of various diseases, including tumor development. Most cancer treatments cause DNA damage and apoptosis. However, cancer cells have the natural ability to repair this damage and inhibit apoptosis, ultimately leading to the development of drug resistance. Therefore, investigating the mechanism of DNA damage may contribute markedly to the future treatment of cancer. The CARMA-BCL10-MALT1 (CBM) complex formed by B cell lymphoma/leukemia 10 (BCL10) regulates apoptosis by activating NF-κB signaling. BCL10 is involved in the formation of complexes that antagonize apoptosis and contribute to cell survival after DNA damage, with cytoplasmic BCL10 entering the nucleus to promote DNA damage repair, including histone ubiquitination and the recruitment of homologous recombination (HR) repair factors. This article reviews the role of BCL10 in cell survival following DNA damage.

Autophagy and its role in gastric cancer.

Autophagy, which is tightly regulated by a series of autophagy-related genes (ATGs), is a vital intracellular homeostatic process through which defective proteins and organelles are degraded and recycled under starvation, hypoxia or other specific cellular stress conditions. For both normal cells and tumour cells, autophagy not only sustains cell survival but can also promote cell death. Autophagy-related signalling pathways include mTOR-dependent pathways, such as the AMPK/mTOR and PI3K/Akt/mTOR pathways, and non-mTOR dependent pathways, such as the P53 pathway. Additionally, autophagy plays a dual role in gastric carcinoma (GC), including a tumour-suppressor role and a tumour-promoter role. Long-term Helicobacter pylori infection can impair autophagy, which may eventually promote tumourigenesis of the gastric mucosa. Moreover, Beclin1, LC3 and P62/SQSTM1 are regarded as autophagy-related markers with GC prognostic value. Autophagy inhibitors and autophagy inducers show promise for GC treatment. This review describes research progress regarding autophagy and its significant role in gastric cancer.

Performance of novel infection phase-dependent antigens in syphilis serodiagnosis and treatment efficacy determination.

OBJECTIVE: The objective of this study was to screen new antigens for syphilis serodiagnosis. METHODS: First, we determined whether the Treponema pallidum proteins Tp0971, Tp0768 and Tp0462 were infection phase-dependent antigens by observing serum reactivity differences in New Zealand rabbits infected with activated or inactivated T. pallidum. A non-infection phase-dependent antigen, the Tp92 membrane protein, was used as the negative control. Next, Tp0971-, Tp0768- and Tp0462-based ELISA was performed on 2138 human serum samples and compared with the T. pallidum passive particle agglutination assay (TPPA) and LiZhu™ Tp-ELISA. In addition, another 60 paired serum samples from patients at follow-up were analysed to evaluate the relationships between titre changes and differences in the A450 nm values of the Tp0971, Tp0768, Tp0462 and Tp92 antibodies measured by ELISA. RESULTS: Compared with Tp92 (negative control), Tp0971, Tp0768 and Tp0462 were determined to be infection phase-dependent antigens. Compared with those of the TPPA, the sensitivities of Tp0971-, Tp0768- and Tp0462-based ELISA were 96.4%, 96.9% and 93.0%, respectively, and the specificities were 97.7%, 95.4% and 98.9%, respectively, resulting in consistencies of 97.1%, 96.2% and 95.9%, respectively. Compared with those of the LiZhu™ Tp-ELISA, the consistencies of Tp0971-, Tp0768- and Tp0462-based ELISA were 95.1%, 94.2% and 94.0%, respectively, with kappa values of 0.902, 0.884 and 0.880, respectively. Tp0971, Tp0768 and Tp0462 demonstrated high sensitivities and specificities, as well as high conformity to the TPPA and LiZhu™ Tp-ELISA. Moreover, a significantly positive Spearman rank correlation coefficient (0.82,*P < 0.05) was found between the difference in the A450 nm values of the Tp0971 antibody and the RPR titre change. CONCLUSION: The infection phase-dependent antigens Tp0971, Tp0768 and Tp0462 are promising for syphilis diagnosis, and Tp0971 may be utilized to monitor curative effects during syphilis treatment.

Immunogenicity and protective efficacy against Treponema pallidum in New Zealand rabbits immunized with plasmid DNA encoding flagellin.

Plasmid DNA encoding flagellin FlaB3 was used as a vaccination candidate for the evaluation of immunogenicity and protection against Treponema pallidum subsp. pallidum dissemination. First, intramuscular injection of the flagellin encoded by the plasmid DNA into New Zealand rabbits elicited both humoral and cellular immune responses. Total IgG production increased in response to flagellin. In addition, serum IFN-γ secretion and CD8+ cells were substantially greater in the rabbits immunized with the plasmid encoding flagellin FlaB3 than those in the rabbits immunized with recombinant flagellin. The flagellin encoded by the plasmid DNA induced significant upregulation of serum IL-6 and IL-8 compared to that of the control rabbits. Subsequently, intradermal challenge of the vaccinated New Zealand rabbits with 1 × 107T. pallidum resulted in a significant reduction of the bacterial organ burden in the blood, liver, spleen, and testicles in the flagellin plasmid DNA-vaccinated rabbits. Furthermore, the histopathological analysis demonstrated that the rabbits immunized with the plasmid DNA-encoded flagellin (FlaB3) showed better immune protection. These findings provide evidence that plasmid DNA-encoded flagellin (FlaB3) may be useful as a potential immunization route for future development of a vaccine to inhibit T. pallidum dissemination in related animals.

Intramuscular primary immunization by nucleic acid vaccine pcDNA/Gpd-IL-2 and enhanced immunization with mucosal adjuvant CpG-ODN and Gpd-IL-2 recombinant protein effectively induced strong mucosal immune responses and immune protective effects against Treponema pallidum skin infection.

The present study aimed to evaluate the immune effect of intramuscular primary immunization by the nucleic acid vaccine pcDNA/glycerophosphodiester phosphodiesterase-interleukin-2 (pcDNA/Gpd-IL-2) and enhanced immunization 2 weeks later with the combination of mucosal adjuvant CpG-oligodeoxynucleotides (ODN) and Gpd-IL-2 recombinant protein on skin infection caused by Treponema pallidum (Tp) in New Zealand rabbits. At week 8 following immunization, MTT assay was used to detect spleen cell proliferation, while enzyme-linked immunosorbent assay was performed to detect the cytokine and secretory immunoglobulin A (SIgA) levels. At week 10 after primary immunization, rabbits were inoculated with 105 Tp (Nichols strain). Alterations in the skin redness, swelling and ulceration were recorded for 0-60 days. In addition, positive rate of Tp in skin lesions and ulcer formation rate were examined using dark field and silver staining. The results indicated that intramuscular primary immunization by nucleic acid vaccine pcDNA/Gpd-IL-2 followed by enhanced immunization via nasal feeding with mucosal adjuvant CpG-ODN and Gpd-IL-2 recombinant protein induced the higher levels of Tp Gpd specific antibodies, increased the secretion of IL-2 and interferon-γ, and promoted the proliferation of T cells in the first 8 weeks after immunization. Furthermore, this immunization strategy stimulated the production of mucosa specific SIgA antibody. Thus, this strategy led to the lowest Tp positive and ulcer formation rates at the Tp infection sites, as well as healing of skin lesions on the earliest time point (day 42). In conclusion, immunization by nucleic acid vaccine pcDNA/Gpd-IL-2 followed by enhanced immunization with a combination of mucosal adjuvant CpG-ODN and Gpd-IL-2 recombinant protein is an effective immune strategy to induce strong mucosal immune responses and immune protective effects.

The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL-8 secretion.

Treponema pallidum is the pathogen that causes syphilis, a sexually transmitted disease; however, the pathogenic mechanism of this organism remains unclear. Tp92 is the only T. pallidum outer membrane protein that has structural features similar to the outer membrane proteins of other Gram-negative bacteria, but the exact functions of this protein remain unknown. In the present study, we demonstrated that the recombinant Tp92 protein can induce human mononuclear cell death. Tp92 mediated the human monocytic cell line derived from an acute monicytic leukemia patient (THP-1) cell death by recognizing CD14 and/or TLR2 on cell surfaces. After the stimulation of THP-1 cells by the Tp92 protein, Tp92 may induce atypical pyroptosis of THP-1 cells via the pro-caspase-1 pathway. Meanwhile, this protein caused the apoptosis of THP-1 cells via the receptor-interacting protein kinase 1/caspase-8/aspase-3 pathway. Tp92 reduced the number of monocytes among peripheral blood mononuclear cells. Interestingly, further research showed that Tp92 failed to increase the tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-10, IL-18 and monocyte chemotactic protein 1 (MCP)-1 levels but slightly elevated the IL-8 levels via the Nuclear Factor (NF)-κB pathway in THP-1 cells. The data suggest that Tp92 recognizes CD14 and TLR2, transfers the signal to a downstream pathway, and activates NF-κB to mediate the production of IL-8. This mechanism may help T. pallidum escape recognition and elimination by the host innate immune system.

Screening and identification of immunoactive FlaB protein fragments of Treponema pallidum for the serodiagnosis of syphilis.

Flagellin is a classical pathogen-associated molecular pattern that can evoke a robust immune response. We have demonstrated previously that three full-length flagellins of Treponema pallidum, namely FlaB1, FlaB2 and FlaB3, did have diagnostic value in the serodiagnosis of syphilis. Here, we selected and constructed three recombinant fragments of each complete FlaB, both the conserved N-terminal and the C-terminal region, and the middle variable part, with the goal of exploring fragments unique to Treponema pallidum for use as antigen targets in a fragment-based serological test. The diagnostic performance of fragments was evaluated using different panels of serum specimens (= 332) by indirect IgG enzyme-linked immunosorbent assay. The data showed that all the conserved fragments exhibited excellent sensitivities (91.1-95.0%) but poor specificities (64.1-78.4%), while the three middle regions demonstrated higher sensitivities and specificities for detecting IgG antibody, with 92.7% and 96.1% for FlaB1M ('B1M'), 91.6% and 94.8% for B2M, and 95.0% and 100% for B3M, respectively. In comparison, the sensitivity and specificity of Architect Syphilis TP was found to be 95.5% and 94.8%, respectively. These findings revealed that the middle portion of each FlaB had epitopes specific for Treponema pallidum and identified B3M as a promising candidate antigen for the serodiagnosis of syphilis.

Development and Evaluation of a Loop-Mediated Isothermal Amplification Assay for the Detection of Treponema pallidum DNA in the Peripheral Blood of Secondary Syphilis Patients.

Secondary syphilis (SS) has always been puzzling for the clinicians because of the similarity of the appearance of skin rashes with other dermatoses. Serological assays are useful, but less sensitive at an early stage of SS or when patients are immunodeficient. Therefore, there is an urgent need to develop a rapid and effective tool for the diagnosis of SS, which may play an important role in the control of epidemic syphilis outbreaks. In this study, we evaluated a loop-mediated isothermal amplification (LAMP) assay, targeting gene encoding the basic membrane protein of Treponema pallidum, to detect the presence of circulating T. pallidum DNA in the blood of SS patients. The specificity of LAMP was validated using three strains of Spirochaetales and six common clinical bacteria. The clinical applicability of LAMP assay was assessed using 642 blood samples from clinically suspected SS patients and 80 samples from healthy blood donors, showing a sensitivity of 82.1% and a specificity of 100.0% in the diagnosis of SS. Thus, our results indicate that the LAMP can be used as a supplementary method for the diagnosis of SS.

A preliminary study on the proinflammatory mechanisms of Treponema pallidum outer membrane protein Tp92 in human macrophages and HMEC-1 cells.

AIMS: To determine proinflammatory mechanisms of Treponema pallidum outer membrane protein Tp92 in the early syphilis infection in human macrophages and HMEC-1 cells. METHODS: Recombinant Tp92 protein was used to stimulate target human macrophages and HMEC-1 cells. PDTC (Pyrrolidinedithiocarbamic acid), SB202190 and Z-YVAD-FMK were used to block the MyD88/NF-κB, MAPKs/p38 and NLRP3/Caspase-1 pathway, respectively. TNF-α, IL-1ß, IL-6, IL-8,NLRP3, casepase-1 were detected by ELISA or Western blot. Lactate dehydrogenase (LDH) activity was measured. RESULTS: Tp92 protein could significantly induced the secretion of proinflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-8 in HMEC-1 cells, but not in macrophages except IL-8. When MyD88/NF-κB pathway was blocked, differences in the secretion of TNF-α, IL-6 and IL-1ß levels and LDH enzyme activity between Tp92 group and Tp92 + PDTC group were not significant (P > 0.05) in HMEC-1 cells and macrophages except IL-8(P < 0.05). When MAPKs/p38 pathway was blocked, differences in the secretion of TNF-α, IL-1ß, IL-6 and IL-8 and LDH enzyme activity both Tp92 group and Tp92 + SB2010190 group were not significant (P > 0.05) in HMEC-1 cells and macrophages. In contrast, when NLRP3/Caspase-1 pathway was blocked with Z-YVAD-FMK, TNF-α, IL-6 and IL-1ß levels, LDH enzyme activity, and Caspase-1 and NLRP3 protein levels were significantly declined (P < 0.05) in HMEC-1 cells except IL-8(P > 0.05). The LDH enzyme activity in macrophages was decreased before and after Z-YVAD-FMK blocking (P < 0.05),however, differences in the secretion of TNF-α, IL-1ß, IL-6 and IL-8 between Tp92 group and Tp92+Z-YVAD-FMK group in macrophages were not significant (P > 0.05). CONCLUSIONS: Tp92 protein may promote proinflammatory cytokines TNF-α, IL-1ß, IL-6 secretion of HMEC-1 cells, but not in macrophages, and increase the LDH enzyme activity of HMEC-1 cells and macrophages through NLRP3/Caspase-1 pathway. However, Tp92 protein may promote IL-8 secretion of HMEC-1 cells and macrophages through MyD88/NF-κB pathway.