The role of c-Myc in phagocytosis of mycobacteria in human macrophages

Poster Presentation (Doctor’s Session)This journal issue contain proceedings of the CongressMycobacterium tuberculosis is an intracellular pathogen and the causative agent of the disease tuberculosis. Macrophages are the major immunocytes to initiate host immunity against mycobacteria. Among the multiple strategies employ by macrophages to defence against mycobacteria, phagocytosis is the first step. Throughphagocytosis, macrophages could not only clear the pathogens from infection sites, but also present antigens derived from the engulfed bacteria to lymphoid cells. c-Myc is a transcription factor that regulates a variety of target genes. It can form a complex with Max and bind to the enhancer box sequences of the promoter to mediate the transcription. Recently, our group revealed that c-Myc has a potential role in regulating the antimicrobial responses in macrophages. Here, we further revealed that c-Myc may play a positive role in phagocytosis and contribute to host defense to mycobacteria. Pretreatment of c-Myc inhibitor, 10058-F4, could significantly reduce the amount of mycobacteria internalised by macrophages. The acidification of phagolysosome in mycobacteria infected macrophages was also inhibited by 10058-F4. Further investigation showed that macrophages phagocytose mycobacteria in a PI3K/Akt independent pathway. And the action of c-Myc inhibitor does not affect the expression levels of Rho family GTPases. However, we found that 10058-F4 could significantly inhibit phorsphorylation of ERK1/2 kinase, which has been indicated to play a role in FcR mediated phagocytosis in macrophage. In conclusion, c-Myc may play a role in phagocytosis of mycobacteria through regulating phorsphorylation of ERK1/2.published_or_final_versio

HIV-1 Tat dysregulation of KSHV induced immune response through the production of IL-8

Poster PresentationHuman immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) and is a major health issue around the world. HIV is known to induce a number of pathological problems in AIDS patients via the transactivator (Tat) protein that is expressed and released by infected cells. One of the most important function of Tat is the dysregulation of the immune response. IL-8 is a chemokine known to be highly expressed in AIDS patients and Tat plays a major role in its production. IL-8 increases the HIV transmission and replication rate; and plays a role in Kaposi's sarcoma associated herpesvirus (KSHV) infection, which is a major opportunistic pathogen that AIDS patients are at risk to. KSHV is also known to induce the expression of IL-8 in patients, and IL-8 is known to assist tumour development by increasing angiogenesis. In our study, we investigated the role that Tat may have in manipulating the expression of IL-8 induced by KSHV in primary blood monocyte derived macrophages (PBMac). The results showed that pretreatment of PBMac with Tat inhibited the expression of IL-8 induced by KSHV by approximately 40%. We also found that Tat was able to inhibit the phosphorylation of STAT-1 induced by KSHV, and the inhibition of STAT-1 phosporylation was related to the expression of IL-8 induced by KSHV. In conclusion, we found that Tat was able to manipulate the expression of IL-8 induced by KSHV in macrophages, and this inhibition of IL-8 expression was regulated through the STAT-1 related pathways.published_or_final_versio

The role of oncogene in mycobacteria-induced antophagy in human macrophages

Poster PresentationMacrophages are the major immunocytes to initiate both innate and adaptive immune responses against Mycobacterium tuberculosis (Mtb), a causative agent of tuberculosis. Upon mycoabcteria infection, macrophages could eliminate the intracellular bacteria through different cell death pathways, including apoptosis and autophagy. c-Myc is a transcription factor that regulates a variety of target genes and control different cellular functions such as proliferation and immune resposnse. Recently, our group revealed that c-Myc has a potential role in regulating the antimicrobial responses in macrophages. Here we use BCG, a live attenuated strain of Mycobacterium bovis, which is similar to Mtb in antigenic composition, as a model to study the role of c-Myc in regulating mycobacteria-induced autophagy. We first investigated the role of c-Myc in BCG-induced LC3BII levels. Knocking down c-Myc by siRNA could decrease BCG-induced LC3BII levels. We found that BCG-induced autophagy is dependent on JNK and p38 and independent on PI3K or ERK pathways. And knocking down of c-Myc could significantly inhibit phosphorylation of p38. In conclusion, c-Myc may play a positive role in mycobacteria-induced autophagy in human macrophages.published_or_final_versio

Pharmacological Effects of Active Compounds on Neurodegenerative Disease with Gastrodia and Uncaria Decoction, a Commonly Used Poststroke Decoction

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A role for STAT3 in IL-10 downregulation of IFN-γ-induced MHC class II molecule expression on primary human blood macrophages

Open Access JournalPaper Presentation: no. 5postprintThe 3rd Annual Scientific Meeting and 4th Annual Meeting of the Hong Kong Society for Paediatric Immunology and Infectious Diseases, Hong Kong, China, 20 March, 2010. In Hong Kong Journal of Psediatrics (New Series), 2010, v. 15 n. 3, p. 25

Dual-specificity protein phosphatase-1 positively regulates the anti-mycobacterial responses

Posters: abstract no. 214Tuberculosis is still prevalent around world. It is caused by Mycobacterium tuberculosis (Mtb). This microbe stimulates monocytes/macrophages leading to the production of specific cytokines for initiating immune responses. Of these cytokines, tumour necrosis factor-alpha (TNF-α) is crucial for inducing the granuloma formation for restricting Mtb dissemination. Using Bacillus Calmette Guerin (BCG) as a model, we showed ...postprintThe 1st Lorne Infection and Immunity Conference, Lorne, Australia, February 2011. In Abstract Book of the 1st Lorne Infection and Immunity Conference, 2011, p. 111, abstract no. 21

Inhibitory effect of Panax Notoginseng (PNG) extracts on the TNF-α-induced MMP-9 activity in cardiomyoblasts

Poster Presentation 10Cardiac remodeling is a compensatory physiologic response to myocardial infarction. The progression of cardiac remodeling may lead to congestive heart failure which has high mortality rate. In this progression, matrix metalloproteinases (MMPs) plays an important role in the degradation of extracellular matrix (ECM) and subsequent ventricular dilation. Therefore, new treatments targeting MMPs are suggested to ...published_or_final_versio

Impact of melamine-tainted milk on foetal kidneys and disease development later in life

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MSH2 c.1452-1455delAATG Is a Founder Mutation and an Important Cause of Hereditary Nonpolyposis Colorectal Cancer in the Southern Chinese Population

Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for ∼2% of all colorectal cancer (CRC) cases and is the most common hereditary CRC syndrome. We have previously reported a high incidence of microsatellite instability (MSI) and germline mismatch repair (MMR) gene mutations in young Hong Kong Chinese with CRC. Ongoing studies at the Hereditary Gastrointestinal Cancer Registry in Hong Kong have revealed a unique germline MSH2 c.1452-1455delAATG mutation that has not been reported in other ethnic groups. Detailed analysis showed that this specific MSH2 mutation constituted 21% of all germline MMR gene mutations and 36% of all MSH2 germline mutations identified. We designed a specific PCR-based diagnostic test on paraffin-embedded tissues and identified this germline mutation in 2 1.5%) of 138 consecutive patients with early-onset CRC (93 million. Further analysis suggested that this founder mutation may date back to between 22 and 103 generations ago. The identification of this MSH2 founder mutation has important implications for the design of mutation-detection strategies for the southern Chinese population. Since there were major emigrations from Hong Kong and Guangdong province during the 19th and 20th centuries, this finding is also significant for Chinese communities worldwide.published_or_final_versio

Array CGH testing in prenatal diagnosis: a promising new service with improved diagnostic yield and shortened reporting time

Eletronic Presentation: abstract no. 904Conference Theme: Enhancing Health - 協作同心‧醫澤社群INTRODUCTION: Array Comparative Genomic Hybridization (aCGH) with genome-wide coverage has proved to be valuable for postnatal and prenatal studies. Traditionally, prenatal diagnosis of chromosomal abnormalities has relied on conventional cytogenetics which required cell culture and chromosome analysis under micro…postprin