Pro‐inflammatory Maternal Cytokine Profile in Preterm Delivery

Nakashima

et al. 2010

American J Rep Immunol

987

863

Citation Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T‐cell paradigm in pregnancy. Am J Reprod Immunol 2010T‐helper (Th) cells play a central role in modulating immune responses. The Th1/Th2 paradigm has now developed into the new Th1/Th2/Th17 paradigm. In addition to effector cells, Th cells are regulated by regulatory T (Treg) cells. Their capacity to produce cytokines is suppressed by immunoregulatory cytokines such as transforming growth factor (TGF)‐β and interleukin (IL)‐10 or by cell‐to‐cell interaction. Here, we will review the immunological environment in normal pregnancy and complicated pregnancy, such as implantation failure, abortion, preterm labor, and preeclampsia from the viewpoint of the new Th1/Th2/Th17 and Treg paradigms.

Section: Th1 ⁄ Th2 ⁄ Th17 and Treg Paradigms In Preterm Labormentioning

confidence: 99%

REVIEW ARTICLE: Th1/Th2/Th17 and Regulatory T‐Cell Paradigm in Pregnancy

Nakashima

et al. 2010

American J Rep Immunol

987

863

Journal of the American Society of Nephrology

“…Although at 48 h a trend was observed in response to AngII treatment toward higher IFN-␥ and lower IL-4 production, the difference between AngII treatment and PHA stimulation alone did not reach statistical significance, which could be due to considerable donor variability. We therefore calculated the IFN-␥:IL-4 ( Figure 2C) for each donor for these two groups as has been done previously (18,19), which demonstrates a significant although modest shift toward greater IFN-␥ production and lesser IL-4 production in response to AngII treatment at 48 h as compared with PHA alone. Of note, the ratio of IFN-␥:IL-4 is thought to be more important in bringing about changes in cytokine signaling, as Th1 and Th2 cytokines are mutually inhibitory (18,19).…”

Section: Angii Treatment Increases the Ratio Of Ifn-␥:il-4 But Not Thmentioning

confidence: 99%

“…We therefore calculated the IFN-␥:IL-4 ( Figure 2C) for each donor for these two groups as has been done previously (18,19), which demonstrates a significant although modest shift toward greater IFN-␥ production and lesser IL-4 production in response to AngII treatment at 48 h as compared with PHA alone. Of note, the ratio of IFN-␥:IL-4 is thought to be more important in bringing about changes in cytokine signaling, as Th1 and Th2 cytokines are mutually inhibitory (18,19). The induction of the inflammatory chemokines CCL2/monocyte chemoattractant protein-1 (MCP-1) and CCL5/RANTES by AngII was also assessed.…”

Section: Angii Treatment Increases the Ratio Of Ifn-␥:il-4 But Not Thmentioning

confidence: 99%

Human T and Natural Killer Cells Possess a Functional Renin-Angiotensin System

Jurewicz¹,

McDermott²,

Sechler³

et al. 2007

200

184

The renin-angiotensin system (RAS) plays an important role in the regulation of inflammation and in the progression of chronic kidney disease. Accumulation of inflammatory cells into the renal parenchyma has been a hallmark of chronic kidney disease; however, little is known concerning the presence and the function of RAS elements in T and natural killer (NK) cells. Here is reported a co-stimulatory effect of angiotensin II (AngII) by showing an augmentation of mitogen and anti-CD3-stimulated T and NK cell proliferation with AngII treatment. Angiotensinogen and AngI also generated the same effect, suggesting that NK and T cells have functional renin and angiotensin-converting enzyme activity. Indeed, they express renin, the renin receptor, angiotensinogen, and angiotensin-converting enzyme by mRNA analysis. Flow cytometric analysis and Western blot revealed angiotensin receptor 2 (AT 2 ) expression in T and NK cells, whereas AT 1 expression was found in T and NK cells and monocytes by Western blot. These receptors were shown to be functional in calcium signaling, chemotaxis, and proliferation. However, AT 1 and AT 2 antagonists alone or in combination were unable to abrogate completely the effects of AngII, suggesting that another AngII receptor may also be functional in leukocytes. This is the first study to show that T and NK cells are fully equipped with RAS elements and are potentially capable of producing and delivering AngII to sites of inflammation. Because their chemotaxis is enhanced by AngII, this creates a potential inflammatory amplification system. B ecause of its hemodynamic effects, angiotensin II (AngII) plays a central role in the progression of chronic kidney diseases (CKD) and ischemic heart disease (1,2). AngII has been shown to be a potent proinflammatory molecule, and the beneficial effects of renin-angiotensin system (RAS) blockade are due not only to lowering BP but also to a reduction in inflammation (3). One of the main features of CKD is the accumulation of inflammatory cells, which plays a crucial role in disease progression (4), and recruitment of macrophages to the kidney through AngII infusion has been reported in various rodent models (5,6). In both diabetic nephropathy and atherosclerosis, monocytes/macrophages have been reported to play a key role (7-9). Monocytes have also been the primary focus of studies that have examined the interaction of AngII and inflammatory cells (10). However, the importance of T, natural killer (NK), and dendritic cells (DC) in inflammation and vascular disease has only recently begun to be appreciated. DC have been shown to present oxidized LDL to T cells, generating autoreactive T cells and promoting arterial injury (11). NK cells participate through the production of proatherogenic cytokines such as IFN-␥ (12). Previous studies on AngII-induced inflammation and its role in kidney disease primarily focused on the induction of inflammatory molecules and the paracrine effects of AngII in vascular remodeling and tissue fibrosis (13,14). Despite these ...

The Journal of Immunology

“…Makhseed et al (13) found significantly higher levels of the type 1 and lower levels of the type 2 cytokines in supernatants of activated peripheral lymphocytes from women undergoing preterm delivery, than in those from healthy pregnant women. Furthermore, abortion-prone women who proceeded to have successful pregnancy were more Th2 biased than abortionprone women who aborted (14).…”

Section: P Eripheral Lymphocytes From Healthy Pregnant Women Express mentioning

confidence: 99%

Molecular Cloning and Immunologic Characterization of a Novel cDNA Coding for Progesterone-Induced Blocking Factor

Polgar

Kispál

Lachmann

et al. 2003

Previous studies from our laboratory showed that the immunomodulatory effects of progesterone are mediated by a 34-kDa protein, named the progesterone-induced blocking factor (PIBF). Lymphocytes of women with threatened abortion fail to produce this factor. Via inducing a Th2 biased cytokine production and blocking of NK activity, PIBF prevents induced pregnancy loss in mice, suggesting that substitution therapy with PIBF could be useful as an alternative treatment of certain forms of recurrent spontaneous abortions. Our study was aimed at mapping the sequence and structure of PIBF coding cDNA and characterizing the encoded protein product. Screening of a human liver cDNA library revealed a 2765-bp clone with a 2271-bp open reading frame. The PIBF1 cDNA encodes a protein of 757 amino acid residues with an 89-kDa predicted molecular mass, which shows no significant amino acid sequence homology with any known protein. PIBF produced via recombinant technique is recognized by the Ab specific for the secreted lymphocyte PIBF Ab, and possesses the biological activities of the secreted lymphocyte PIBF. The full-length PIBF is associated with the nucleus, whereas secretion of shorter forms, such a 34-kDa protein is induced by activation of the cell. The 48-kDa N-terminal part of PIBF is biologically active, and the part of the molecule, responsible for modulating NK activity is encoded by exons 2–4. These data provide an initial step for exploiting the possible diagnostic and therapeutic potential of this immunomodulatory molecule.