A term ''bone-breaking fever'' is used in Chinese medicine to describe the symptoms of patients infected with dengue virus (DV). We examined the significance of the COXprostaglandin pathway in human DC infected by DV. We show that DV infection induced the expression of COX-2 and the production of prostaglandin E 2 (PGE 2 ) in DC, and stimulated the DNA binding of NF-jB and the kinase activity of both IjBa kinase (IKK) a and b. DV infection also activated MAPK and AP-1 signaling. Both IjBa kinase-NF-jB and MAPK-AP-1 were upstream of COX-2 activation. Our investigation into the significance of COX-2-PGE 2 pathway also revealed that DV infection enhances DC migration by inducing CC chemokine receptor 7 (CCR7) expression, and that blocking COX-2 or MAPK activity suppresses DV-induced DC migration. Our data also suggest that PGE 2 can induce CCR7 expression on DC and that antagonists of the PGE 2 receptors EP2 and EP4 suppress DV-induced DC migration. We further show that the increased CCR7 expression was observed in both DV-infected and bystander DC, suggesting the presence of secondary effects in inducing CCR7 expression. Collectively, this study reveals not only the pathways involved in COX-2 synthesis in DV-infected DC but also the autocrine action of PGE 2 on the migration of DV-infected DC.Key words: COX-2 . DC . Dengue virus . Inflammation Supporting Information available online IntroductionDengue viruses (DV) are members of the mosquito-borne flaviviruses that infect humans and cause dengue fever with potential severe outcomes such as dengue hemorrhagic fever and dengue shock syndrome [1,2]. DV infection occurs in most tropical and subtropical areas of the world and has become one of the major concerns for those traveling to these areas [3]. Epidemiological analysis reveals that worldwide the estimated occurrence is around 50-100 million cases for dengue fever yearly and for dengue hemorrhagic fever is about 250-500 thousand cases [4]. Efforts aiming to developing a vaccine have not yet been successful [5]. This may be due to the complicated mechanisms of immunopathogenesis [6,7]. Interestingly, Eur. J. Immunol. 2009. 39: 3413-3422 DOI 10.1002 Immunomodulation 3413 although the members of flaviviruses vary, a recent observation by Moran et al. [8] shows that a subset of residues within an epitope bound to a class II molecule are cross-reactively recognized by CD4 1 TCR.The term ''bone-breaking fever'' has long been used in Chinese medicine to describe the symptoms of DV-infected patients. Accordingly, the activation of COX-2-related signaling pathways may be involved in the pathogenesis of DV infection and thus contributes to the clinical manifestations. One of the products of this pathway, prostaglandin E 2 (PGE 2 ), has been shown to modulate inflammatory reactions [9] and regulate viral replication [10]. Given the important roles of COX-2-PGE 2 in many inflammatory responses on different host cells, it is surprising that the induction of COX-2-PGE 2 has not been consistently observed in experimental vira...

E-C4d levels are useful diagnostic markers for SLE and can serve as biomarkers of disease activity in patients with SLE. However, E-C4d is of limited value in monitoring disease activity in SLE patients with HA.

Primary Sjögren's syndrome (PSS) is an autoimmune disease targeting exocrine glands. It ten times more dominantly affects women than men with an onset peak at menopause. The genetic factor predisposing women to PSS remains unclear. Therefore, we aimed to identify susceptibility loci for PSS in women. We performed genome-wide association study (GWAS) using 242 female PSS patients and 1444 female control in Han Chinese population residing in Taiwan. Replication was conducted in an independent cohort of 178 female PSS and 14,432 control subjects. We identified rs117026326 on GTF2I with GWAS significance (P = 1.10 × 10) and rs13079920 on RBMS3 with suggestive significance (P = 2.90 × 10) associating with PSS in women. The association of RBMS3 was further evidenced by imputation in which rs13072846 (P = 4.89 × 10) was identified and confirmed as female PSS associating SNP within the same LD with rs13079920. PSS pathogenesis involves both immune (effector) and exocrine (target) system. We suggested that while GTF2I is a previously reported associating gene which may function in immune system, RBMS3 is a novel susceptibility gene that predisposes women to PSS potentially through modulating acinar apoptosis and TGF-β signaling in target exocrine system.