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In this study, we interviewed 14 doctoral students from 10 COAMFTE-accredited doctoral programs to learn more about how they experienced their research training and what they might suggest to strengthen the research culture in their training programs. We solicited somewhat unconventional data--metaphors, poetry, free associations, critical experiences--to (a) tap into our participants' underlying thought processes, (b) capture the multifaceted nature of their doctoral research training, and (c) represent the richness of our participants' subjective experiences. The themes we identified reflect both positive and negative research training experiences and suggest several ways that family therapy program faculty might improve their programs' research training and culture.

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Low-grade inflammation contributes to diseases such as atherosclerosis, arthritis, and diabetes. Contributors to low-grade inflammation include circulating microbial products such as lipopolysaccharide (LPS). High plasma levels of LPS cause acute shock, but low levels of LPS predispose individuals to mild inflammatory conditions. This predisposition results from mild expression of pro-inflammatory cytokines without compensating anti-inflammatory modulators, leading to persistent, unresolved inflammation. Despite the clinical importance of chronic inflammation, its underlying mechanisms are poorly understood. Glycogen synthase kinase 3 (GSK3) is implicated in the pro-inflammatory conditioning of innate immunity. We tested whether inhibition of GSK3 and upstream kinases can prevent inflammatory skewing by low dose LPS. We measured the expression of pro-inflammatory IL-6 and anti-inflammatory IL-33 in pre-monocytic THP-1 cells treated with low dose LPS (50 pg/mL) and a GSK3 inhibitor. We observed that while low dose LPS alone induced mild expression of IL-6, GSK3 inhibition skews THP-1 cells into an anti-inflammatory state by augmenting the induction of IL-33 by low dose LPS while diminishing the induction of IL-6. We found that broad inhibition of tyrosine kinases also diminishes IL-6 induction. These observations suggest a complex intracellular circuit that dynamically modulates the expression of pro- and anti-inflammatory mediators upon treatment with low dose LPS.

Monocytes and macrophages can be dynamically programmed into distinct states depending upon the strength of external stimulants. Innate programming may bear significant relevance to the pathogenesis and resolution of human inflammatory diseases. However, systems analyses of the molecular mechanisms responsible for the dynamic programming of innate leukocytes are lacking. In this study, we focused on the macrophage responses to lipopolysaccharide (LPS), a ubiquitous bacterial endotoxin recognized by Toll-like receptor 4 (TLR4). We employed both immortalized human monocytic THP-1 cells and primary murine bone-marrow derived macrophages (BMDM). We observed that varying doses of LPS induce distinct expression profiles of selected pro- and anti- inflammatory cytokines. Lower doses of LPS preferentially suppressed anti-inflammatory mediators, and selectively induced pro-inflammatory mediators. Rising LPS dosages caused a shift in expression profiles, giving rise to double-positive cells. Higher LPS dosages shifted the landscape to anti-inflammatory mediators and drove down the expression of pro-inflammatory mediators. By utilizing BMDM from IRAK-M knockout mice, we identified IRAK-M as a key player in this process, as IRAK-M deletion skews the dynamic responses to varying dosages of LPS. Our study provides a systems view of macrophage programming, and may shed light on our understanding of the dynamic balance between pathogenesis and resolution of inflammatory diseases.