ResultsEvidence collected allows us to propose the following working model. Compromised lymph drainage, reported in IBD, leads to oedema, lymphangiogenesis, impaired immune cell trafficking and lymph leakage. Lymph factor(s) stimulate adipose tissue to proliferate and produce cytokines, which affect immune cell functions and exacerbate inflammation. ConclusionsUnderstanding the lymphatic system's role in immune cell trafficking and immune responses, contribution to fat transport, distribution, metabolism and implication in the pathogenesis of chronic intestinal inflammation may provide the basis for new therapeutic strategies and improved quality-oflife. Alimentary Pharmacology and Therapeutics Aliment Pharmacol Ther INTRODUCTIONThe lymphatic system is a frequently overlooked yet vitally important system in the body. In addition to maintaining tissue fluid homoeostasis, it plays critical roles in immune defence and in metabolic maintenance. Indeed, it functions as an interface between our body and the environment. It is a pre-eminent player in the body's response to pathogens and acts as the physical basis of the immune system by providing conduits and lymph nodes for the presentation of potentially harmful antigens from the environment to immune cells, leading to recognition and initiation of an immune response. It is important for energy storage and metabolic functions, most notably by supplying a route for ingested lipids to be absorbed, stored and metabolized. Finally, it serves as a collective 'garbage dump', where dead cells, bacteria, poisons, toxins and excess fluids are deposited from bodily tissues. Subsequently, it indirectly delivers these substances via the blood to the organs of detoxification including the liver, kidneys, skin, lungs and large colon for eventual elimination. LYMPHATIC SYSTEM, LYMPHATIC PUMPING AND LYMPH FLOWThe lymphatic system is composed of numerous vessels connecting the interstitial tissue space to blood circulation and to lymphoid organs such as lymph nodes, the spleen and other lymphoid structures (e.g. Peyer's patches in the small intestine). The lymphatic vessels, or lymphatics, are widely distributed throughout the body and are organized into a very dense and extensive network. Unlike the cardiovascular system, which is a closed-circuit relying on a central pump to move blood, lymphatic vessels form a one-way system that collects lymph from the extremities by the initial lymphatics, propels it via the pumping action of the collecting lymphatics and empties its contents into the venous circulation. Any deficiencies in this process lead to fluid accumulation in the interstitium, oedema and insurmountable osmotic imbalance.1 Initial lymphatics are blind-ended tubes comprising endothelial cells (e.g. lacteals in intestinal villi), which lie in close proximity to the blood capillaries, picking up fluid and proteins that leave the cardiovascular system to maintain tissue fluid balance. The collecting lymphatic vessels differ from the initial lymphatics in that most have smooth ...

Background The development of the in vitro cell culture model has greatly facilitated the ability to study gene expression and regulation within human tissues. Within the human uterus, the upper (fundal) segment and the lower segment may provide distinct functions throughout pregnancy and during labour. We have established primary cultured human myometrial cells, isolated from both upper and lower segment regions of the pregnant human uterus, and validated them for the purpose of studying human pregnancy and labour. The specific objectives of this study were to monitor the viability and characterize the expression profile using selected cellular, contractile and pregnancy associated markers in the primary cultured human myometrial cells. Labour has been described as an inflammatory process; therefore, the ability of these cells to respond to an inflammatory stimulus was also investigated. Methods Myometrial cells isolated from paired upper segment (US) and lower segment (LS) biopsies, obtained from women undergoing Caesarean section deliveries at term prior to the onset of labour, were used to identify expression of; α smooth muscle actin, calponin, caldesmon, connexin 43, cyclo-oxygenase-2 (COX-2), oxytocin receptor, tropomyosin and vimentin, by RT-PCR and/or immunocytochemistry. Interleukin (IL)-1β was used to treat cells, subsequently expression of COX-2 mRNA and release of interleukin-8 (CXCL8), were measured. ANOVA followed by Bonferroni’s multiple comparisons test was performed. Results We demonstrate that US and LS human myometrial cells stably express all markers examined to at least passage ten (p10). Connexin 43, COX-2 and vimentin mRNA expression were significantly higher in LS cells compared to US cells. Both cell populations respond to IL-1β, demonstrated by a robust release of CXCL8 and increased expression of COX-2 mRNA from passage one (p1) through to p10. Conclusions Isolated primary myometrial cells maintain expression of smooth muscle and pregnancy-associated markers and retain their ability to respond to an inflammatory stimulus. These distinct myometrial cell models will provide a useful tool to investigate mechanisms underlying the process of human labour and the concept of functional regionalization of the pregnant uterus.

Inflammatory mediators, including prostaglandins, cytokines, and chemokines, are strongly implicated in the mechanism of human labor, though their precise roles remain unknown. Here we demonstrate that interleukin 1 beta (IL-1beta) significantly increased the expression and release of interleukin-8 (CXCL8), monocyte chemotactic protein-1 (CCL2), and granulocyte macrophage colony-stimulating factor (CSF2) by primary human myometrial cells. However, this effect was repressed by prostaglandin E(2) (PGE(2)). As PGE(2) can activate four distinct PGE(2) receptors (EP(1), EP(2), EP(3), and EP(4)) to elicit various responses, we sought to define the EP receptor(s) responsible for this repression. Using selective EP receptor agonists and a selective EP(4) antagonist, we show that PGE(2) mediates the repression of IL-1beta-induced release of CXCL8, CCL2, and CSF2 via activation of the EP(2) and EP(4) receptors. The use of siRNA gene-specific knockdown further confirmed a role for both receptors. Real-time RT-PCR demonstrated that EP(2) was the most highly expressed of all four EP receptors at the mRNA level in human myometrial cells, and immunocytochemistry showed that EP(2) protein is abundantly present throughout the cells. Interestingly, PGE(2) does not appear to reduce mRNA expression of CXCL8, CCL2, and CSF2. Our results demonstrate that PGE(2) can elicit anti-inflammatory responses via activation of the EP(2) and EP(4) receptors in lower segment term pregnant human myometrial cells. Further elucidation of the EP receptor-mediated signaling pathways in the pregnant human uterus may be beneficial for optimizing the maintenance of pregnancy, induction of labor or indeed treatment of preterm labor.

Within a dynamic health research environment with trends toward increasing accountability, governments and funding agencies have placed increased emphasis on knowledge translation (KT) as a way to optimize the impact of research investments on health outcomes, research products and health service delivery. As a result, there is an increasing need for familiarity with the principles of KT frameworks and components of KT strategies. Accordingly, health research trainees (graduate students and post-doctoral fellows) must be supported to enhance their capacity to understand KT principles and the practicalities of implementing e ective KT practices.In this paper, the unique opportunities and challenges that trainees within an interdisciplinary research team encounter when they begin to understand and apply constructive and relevant KT practices are considered. Our commentary is based on trainee experiences within the Preterm Birth and Healthy Outcomes Team (PreHOT), an interdisciplinary research team.

Prostaglandins are implicated in the labor process, yet the precise role and regulation of the prostaglandin pathway remains to be elucidated. The first step in the pathway is cleavage of membrane phospholipids by phospholipase A 2 (PLA 2 ). Previous work demonstrated upregulation of secretory PLA 2 (sPLA 2 )-IIA with labor in human myometrium, and recent evidence shows that there are numerous PLA 2 isoforms. The present study investigates the potential of additional sPLA 2 isoforms during pregnancy and labor. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry were used to determine sPLA 2 expression and localization. Results show the presence of sPLA 2 -IID in amnion, chorion, placenta, decidua, and myometrium. Expression of sPLA 2 -IID in decidua was significantly decreased in term labor compared to nonlabor patients, whereas no significant labor-associated changes were observed in other gestational tissues. Secretory PLA 2 -IID was localized within chorion fibroblasts, placenta trophoblasts, decidual cells, and in myometrial smooth muscle cells. In primary decidual cell cultures, interleukin (IL) 10 (IL-10) increased sPLA 2 -IID messenger RNA (mRNA) expression, while IL-1b had no effect on sPLA 2 -IID mRNA expression. In conclusion, decreased expression of sPLA 2 -IID in the decidua at labor indicates that it is unlikely to contribute to increased prostaglandin production during labor. However, increased expression of sPLA 2 -IID, induced by IL-10, suggests that sPLA 2 -IID may play an important anti-inflammatory role at the maternal-fetal interface. Nevertheless, precise functions of sPLA 2 -IID within the human uterus remain to be determined.