Niluka Gunawardhana - Academia.edu (original) (raw)

Papers by Niluka Gunawardhana

Journal of Microbiology and Biotechnology, Oct 28, 2016

Frontiers in Cellular and Infection Microbiology, Jan 15, 2018

Helicobacter pylori is associated with hypergastrinemia, which has been linked to the development... more Helicobacter pylori is associated with hypergastrinemia, which has been linked to the development of gastric diseases. Although the molecular mechanism is not fully understood, H. pylori is known to modulate the Erk pathway for induction of gastrin expression. Herein we found that an epidermal growth factor (EGF) receptor kinase inhibitor significantly blocked H. pylori-induced gastrin promoter activity, suggesting involvement of EGF receptor ligands. Indeed, H. pylori induced mRNA expression of EGF family members such as amphiregulin, EGF, heparin-binding EGF-like growth factor (HB-EGF), and transforming growth factor-α. Of these, specific siRNA targeting of HB-EGF significantly blocked H. pylori-induced gastrin expression. Moreover, H. pylori induced HB-EGF ectodomain shedding, which we found to be a critical process for H. pylori-induced gastrin expression. Thus, we demonstrate a novel role for human mature HB-EGF in stimulating gastrin promoter activity during H. pylori infection. Further investigation using specific siRNAs targeting each isoform of Raf, Mek, and Erk elucidated that the mechanism underlying H. pylori-induced gastrin expression can be delineated as the sequential activation of HB-EGF, the EGF receptor, C-Raf, Mek1, and the Erk2 molecules in the MAPK pathway. Surprisingly, whereas Erk2 acts as a potent activator of gastrin expression, siRNA knockdown of Erk1 induced gastrin promoter activity, suggesting that Erk1 typically acts as a repressor of gastrin expression. Elucidation of the mechanism of gastrin modulation by HB-EGF-mediated EGF receptor transactivation should facilitate the development of therapeutic strategies against H. pylori-related hypergastrinemia and consequently gastric disease development, including gastric cancers.

한국미생물학회 학술대회논문집, Apr 1, 2015

Scientific Reports, Aug 1, 2019

Dept. of Dental Science/박사Introduction: Helicobacter pylori is a gram negative bacterium, special... more Dept. of Dental Science/박사Introduction: Helicobacter pylori is a gram negative bacterium, specialized in the colonization of human stomach and a major risk factor for development of gastric cancers. It has been observed in H. pylori-infected patients that gastrin secretion stimulated by H. pylori leads to hypergastrinemia and as consequences, chronic gastritis and gastric atrophy. Gastrin is an important hormone in human stomach which mainly regulates gastric acid secretion. In addition, it is also involved in growth and differentiation of gastric epithelial cells. H. pylori-induced hypergastrinemia is known as a major risk factor for the development of gastric cancers. Moreover, it has been described that H. pylori modulates mitogen activated protein (MAP) kinase pathway, one of the major epithelial cell signaling pathways in humans, which regulates gastrin expression. However, the molecular mechanism, especially how each isotypes of mitogen activated protein kinase pathway are inv...

Scientific Reports, 2019

Infection with CagA+ Helicobacter pylori strains is linked to an increased risk for gastric disea... more Infection with CagA+ Helicobacter pylori strains is linked to an increased risk for gastric diseases, including gastric cancer. Recent evidence indicates that dynamic expansion and contraction of cagA copy number may serve as a novel mechanism to enhance disease development. Herein, comparative genomic analysis divided hpEurope into two groups: hpEurope/type-A and type-B. Only hpEurope/type-B displayed the multi-cagA genotype. Further analysis showed that cagPAI appears to have been independently introduced into two different H. pylori types, termed pre-type-A and pre-type-B, which consequently evolved to cagPAI type-A and type-B, respectively; importantly, all multi-cagA genotype strains displayed cagPAI type-B. Two direct cagA-flanking repeats of a genetic element termed CHA-ud were essential for the multi-cagA genotype in strain PMSS1 (hpEurope/type-B and cagPAI type-B). Furthermore, introduction of this genetic element into strain G27 (hpEurope/type-A and cagPAI type-A) was suff...

Frontiers in cellular and infection microbiology, 2017

mBio, Feb 21, 2017

Infection with Helicobacter pylori is a major risk factor for development of gastric disease, inc... more Infection with Helicobacter pylori is a major risk factor for development of gastric disease, including gastric cancer. Patients infected with H. pylori strains that express CagA are at even greater risk of gastric carcinoma. Given the importance of CagA, this report describes a new molecular mechanism by which the cagA copy number dynamically expands and contracts in H. pylori Analysis of strain PMSS1 revealed a heterogeneous population in terms of numbers of cagA copies; strains carried from zero to four copies of cagA that were arranged as direct repeats within the chromosome. Each of the multiple copies of cagA was expressed and encoded functional CagA; strains with more cagA repeats exhibited higher levels of CagA expression and increased levels of delivery and phosphorylation of CagA within host cells. This concomitantly resulted in more virulent phenotypes as measured by cell elongation and interleukin-8 (IL-8) induction. Sequence analysis of the repeat region revealed three ...

Journal of microbiology and biotechnology, Jan 19, 2016

Areca nut (AN) chewing is a habit in many countries in Central, Southern, and Southeast Asia. It ... more Areca nut (AN) chewing is a habit in many countries in Central, Southern, and Southeast Asia. It is strongly associated with the occurrence of oral, pharyngeal, and esophageal cancer as well as systemic inflammation. However, the association between AN intake and the development of gastric lesions has not yet been identified. The aim of this study was to investigate the effect of AN on gastric diseases using a mouse model for Helicobacter pylori infection. We studied four groups of mice: those fed a normal diet (ND), those fed a diet containing 2.5% AN (AD), those fed a normal diet and infected with H. pylori PMSS1 strain (ND/HP), and those fed a diet containing 2.5% AN and infected with H. pylori PMSS1 strain (AD/HP). Food intake and body weight were monitored weekly during the experiments. At 10 weeks, the mice were sacrificed, and stomach weight, H. pylori colonization, and gastric inflammation were evaluated. Stomach weight had increased significantly in the ND/HP and AD/HP grou...

Journal of microbiology (Seoul, Korea), 2016

Mammalian γ-glutamyltranspeptidase (GGT) has been identified as a bone-resorbing factor. Since GG... more Mammalian γ-glutamyltranspeptidase (GGT) has been identified as a bone-resorbing factor. Since GGT of Bacillus subtilis exhibits similarity in their primary structure and enzymatic characteristics with mammalian GGTs, the bone-resorbing activity of bacterial GGT was examined in this study. Osteoclastogenesis was performed in a co-culture system of mouse calvaria-derived osteoblasts and bone marrow cells. A conditioned medium from GGT-overproducing B. subtilis culture showed significantly higher activity of osteoclast formation than a conditioned medium from wild-type B. subtilis culture. Recombinant GGT (rGGT) of wild-type B. subtilis and an enzymatic activity-defected rGGT of B. subtilis 2288 mutant were expressed in Escherichia coli and purified using His tag. Both purified rGGTs induced similar levels of osteoclastogenesis, suggesting that B. subtilis GGT possesses virulent bone-resorbing activity and its activity is probably independent of its enzymatic activity. Furthermore, a ...

Journal of Oral Pathology & Medicine, 2010

BACKGROUND: The aim of this retrospective study was to analyse the relative prevalence and the cl... more BACKGROUND: The aim of this retrospective study was to analyse the relative prevalence and the clinico-pathological characteristics of mandibular and maxillary ameloblastomas in Sri Lanka. METHODS: Clinico-pathological features of a total of 286 cases of ameloblastomas were analysed. RESULTS: Out of the 286 cases, 87.8% (251/286) of ameloblastomas occurred in the mandible, while 10.8% (31/286) occurred in the maxilla indicating a ratio of 8:1. In the mandible, 54% (136/251), 40% (100/251) and 6% (15/ 251) of tumours and in the maxilla, 23% (7/31), 48% (15/ 31) and 29% (9/31) of tumours were solid/multicystic ameloblastomas (SMA), unicystic ameloblastomas (UA) and desmoplastic ameloblastomas (DA) respectively. No gender predilection was observed in mandibular or maxillary ameloblastomas. Most of the lesions were observed in 2nd to 5th decade of life (mean age 33.2 years). No differences between mandibular and maxillary ameloblastomas were observed with reference to overall cellularity and mitotic activity. Solid/multicystic and UAs showed a predilection to posterior region, while DAs were frequently found in the anterior region of both jaws. Twenty-one percentage (60/286) of ameloblastomas presented with recurrences, and 94% (34/36) of these recurrences were observed in cases treated conservatively. CONCLUSION: In conclusion, mandibular ameloblastomas were more prevalent than maxillary ameloblastomas, while no differences were observed in age or gender distribution between the mandibular and maxillary ameloblastomas. However, higher proportion of DAs and UAs was observed in the maxilla compared with some of the other studies. SMA should be treated with resection to prevent recurrences.

Acta Odontologica Scandinavica, 2013

This study examined the effect of the interaction between periodontitis and type 1 diabetes melli... more This study examined the effect of the interaction between periodontitis and type 1 diabetes mellitus on alveolar bone, mandibular condyle and tibia in animal models. Rats were divided into normal, periodontitis, diabetic and diabetic with periodontitis groups. After injection of streptozotocin to induce diabetes, periodontitis was induced by ligation of both lower-side first molars for 30 days. Alveolar bone loss and trabecular bone volume fraction (BVF) of the mandibular condyle and tibia were estimated via hematoxylin and eosin staining and micro-computed tomography, respectively. Osteoclastogenesis of bone marrow cells isolated from tibia and femur was assayed using tartrate-resistant acid phosphatase staining. The cemento-enamel junction to the alveolar bone crest distance and ratio of periodontal ligament area in the diabetic with periodontitis group were significantly increased compared to those of the periodontitis group. Mandibular condyle BVF did not differ among groups. The BVF of tibia in the diabetic and diabetic with periodontitis groups was lower than that of the normal and periodontitis groups. Osteoclastogenesis of bone marrow cells in the diabetic groups was higher than that in the non-diabetic groups. However, the BVF of tibia and osteoclastogenesis in the diabetic with periodontitis group were not significantly different than those in the diabetic group. Type 1 diabetes mellitus aggravates alveolar bone loss induced by periodontitis, but periodontitis does not alter the mandibular condyle and tibia bone loss induced by diabetes. Alveolar bone, mandibular condyle and tibia may have different responses to bone loss stimuli in the diabetic environment.

Journal of Investigative and Clinical Dentistry, 2013

Diagnostic criteria that have been specified for unicystic ameloblastomas (UAs) are not always he... more Diagnostic criteria that have been specified for unicystic ameloblastomas (UAs) are not always helpful to differentiate these cystic tumors from common odontogenic cysts. The aim of this study therefore was to identify additional histopathological features (other than the features considered for the diagnosis of UA at present) that would be helpful to differentiate UA from odontogenic cysts. One hundred histopathologically confirmed unicystic ameloblastomas and 20 cases each of radicular, inflamed dentigerous and non-inflamed dentigerous cysts were selected. Histopathological features of the UAs that are not used as diagnostic criteria at present were identified. Hyperplastic arcading epithelial proliferations with stellate-reticulum-like and vacuolated cells were always seen associated with inflammation in odontogenic cysts, while in UA plexiform-like areas were also seen without inflammation (P &amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In addition, a spiky rete pattern was observed in non-inflamed UA while this pattern was observed only in inflamed odontogenic cysts. Furthermore, spiky retes together with subepithelial hyalinization were usually observed in UAs while only subepithelial hyalinization was observed in non-inflamed dentigerous cysts. Combinations of histopathological features were identified to differentiate non-inflamed UA from common odontogenic cysts. However, presence of inflammatory changes in UA precludes the use of features identified in the present study for diagnostic purposes.