The purpose of this study was to determine if progesterone has an effect on fetoplacental artery production of inflammatory cytokines.
Chorionic plate arteries were dissected from 5 placentas obtained from normal pregnancies after delivery at term. Arteries were incubated in Dulbecco's modified Eagle's medium (DMEM) alone, DMEM and lipopolysaccharide (LPS), DMEM with progesterone (P4), and DMEM with P4 and LPS. Samples of the tissue culture media were collected and evaluated for interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10) by immunoassay.
There was a significant decrease in the production of IL-6 in P4-exposed fetoplacental arteries after LPS stimulation (P < .001). IL-10 and TNF-alpha levels were similar in control and treatment groups after LPS exposure.
Pretreating fetoplacental arteries with P4 significantly decreased the production of IL-6 after LPS stimulation without altering the production of TNF-alpha or IL-10.
"Therefore, it is likely that paracrine factors such as cytokines and chemokines act as effectors of steroid hormones, thus enabling systemic immune modulation in the absence of leukocyte steroid receptors. In fact, there is ample evidence in the literature for regulation of immune function by progesterone through its effect on smooth muscle, stromal, and perivascular cells (Gotkin et al., 2006; Hardy et al., 2006; Luk et al., 2010; Shields et al., 2005; Shynlova et al., 2008). Due to its multiple cellular targets, a comprehensive dissection of cell specific signaling, as well as direct downstream targets of PR, is necessary to understand the multiple immune-modulatory functions of progesterone. "
[Show abstract][Hide abstract] ABSTRACT: Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues.
"Cytokines are recognized as small and nonstructural proteins , which are pleiotropic and have multiple diverse biological activities . Several studies have demonstrated that progesterone could modulate inflammatory cytokine production in vivo and vitro  . As revealed by He et al. , post-TBI progesterone administration might attenuate the production of proinflammatory cytokines, such as IL- 1β and TNF-α, in the injured brain. "
[Show abstract][Hide abstract] ABSTRACT: We have previously shown that traumatic brain injury (TBI) can induce an upregulation of nuclear factor kappa B (NF-kappaB) and proinflammatory cytokines in the gut, which play an important role in the pathogenesis of acute gut mucosal injury mediated by inflammation. In this work, we investigated whether progesterone administration modulated intestinal NF-kappaB activity and proinflammatory cytokines expression after TBI in male rats. As a result, we found that administration of progesterone following TBI could decrease NF-kappaB binding activity, NF-kappaB p65 protein expression, and concentrations of interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) in the gut. TBI-induced damages of gut structure were ameliorated after progesterone injections. The results of the present study suggest that the therapeutic benefit of post-TBI progesterone injections might be due to its inhibitory effects on intestinal NF-kappaB activation and proinflammatory cytokines expression.
Mediators of Inflammation 02/2007; 2007:93431. DOI:10.1155/2007/93431 · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bessel beams can be used as optical tweezers, to trap and manipulate small particles, including biological specimens. Here we demonstrate the use of such beams to trap and manipulate particles simultaneously that may reside in completely separate sample chambers, separated by distances that preclude trapping with a Gaussian beam. This also demonstrates another property of the Bessel beam, in that since it is a set of rings it can trap both low and high refractive index particles. The distance behind the particle that the Bessel beam reconstructs is dependent on the properties of the particle, and this may be useful in cell characterisation. We also demonstrate the generation of more complex patterns of nondiffracting light beams, by using interfering Bessel beams. We generate these by using a Mach-Zender interferometer in which each of the arms has a Laguerre-Gaussian beam of differing handedness.
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