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Bacterial lipopolysaccharides form procollagen-endotoxin complexes that trigger cartilage inflammation and degeneration: implications for the development of rheumatoid arthritis
1 Institute of Indoor Diagnostics, Marconistrasse 23, D-40589 Duesseldorf, Germany
2 Musculoskeletal Research Group, Institute of Anatomy, Ludwig Maximilian University Munich, Pettenkoferstrasse 11, D-80336 Munich, Germany
3 Medical Research Council-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Arthritis Research UK Pain Centre, Arthritis Research UK Centre for Sport, Exercise, and Osteoarthritis, Faculty of Medicine and Health Sciences, The University of Nottingham, Sutton Bonington Campus, Sutton Bonington, LE12 5RD, Nottingham, United Kingdom
4 Center of Excellence in Genomic Medicine Research (CEGMR), King AbdulAziz University, Jeddah 21589, Kingdom of Saudi Arabia
5 Schools of Pharmacy and Life Sciences, University of Bradford, Richmond Road, Bradford, BD7 1DP, United Kingdom
6 German Heart Institute Berlin, Department of Thoracic and Cardiovascular Surgery, Laboratory for Tissue Engineering, Augustenburger Platz 1, 13353 Berlin, Germany
Arthritis Research & Therapy 2013, 15:R111 doi:10.1186/ar4291Published: 10 September 2013
We have previously reported that bacterial toxins, especially endotoxins such as lipopolysaccharides (LPS), might be important causative agents in the pathogenesis of rheumatoid arthritis (RA) in an in vitro model that simulates the potential effects of residing in damp buildings. Since numerous inflammatory processes are linked with the nuclear factor-κB (NF-κB), we investigated in detail the effects of LPS on the NF-κB pathway and the postulated formation of procollagen-endotoxin complexes.
An in vitro model of human chondrocytes was used to investigate LPS-mediated inflammatory signaling.
Immunoelectron microscopy revealed that LPS physically interact with collagen type II in the extracellular matrix (ECM) and anti-collagen type II significantly reduced this interaction. BMS-345541 (a specific inhibitor of IκB kinase (IKK)) or wortmannin (a specific inhibitor of phosphatidylinositol 3-kinase (PI-3K)) inhibited the LPS-induced degradation of the ECM and apoptosis in chondrocytes. This effect was completely inhibited by combining BMS-345541 and wortmannin. Furthermore, BMS-345541 and/or wortmannin suppressed the LPS-induced upregulation of catabolic enzymes that mediate ECM degradation (matrix metalloproteinases-9, -13), cyclooxygenase-2 and apoptosis (activated caspase-3). These proteins are regulated by NF-κB, suggesting that the NF-κB and PI-3K pathways are involved in LPS-induced cartilage degradation. The induction of NF-κB correlated with activation of IκBα kinase, IκBα phosphorylation, IκBα degradation, p65 phosphorylation and p65 nuclear translocation. Further upstream, LPS induced the expression of Toll-like receptor 4 (TLR4) and bound with TLR4, indicating that LPS acts through TLR4.
These results suggest that molecular associations between LPS/TLR4/collagen type II in chondrocytes upregulate the NF-κB and PI-3K signaling pathways and activate proinflammatory activity.


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Can Eco Fashion Go Mainstream? H&M And Amber Valletta Say Yes
"I'm very excited to work with the H&M Conscious campaign, because we share the same values about sustainability," explains the supermodel. "This collection shows that you can be as mindful about people and the environment as fashion conscious. I simply love the designs and the fact that all the pieces are made with organic, recycled and cellulose fabrics shows that you don't need to compromise fashion for sustainability anymore."
The brand has also joined forces with design think tank and sustainable fashion brand Ever Manifesto to a create a capsule collection called Conscious Exclusive. This tight edit of boho-inspired pieces will be available at 150 stores worldwide and online. Sadly both collections won't be available to buy 'til April 10, 2014. Click through to watch the video of Valletta and the designers Elizabeth von Guttman and Alexia Niedzielski from Ever Manifesto discuss this exciting project.

subset: commoncrawl


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Archive for Thursday, October 26, 2006
Masterpiece theater
Girls team, Burns and Chino to join Graff in Wamego
It's 10-second battles.
The girls four-kilometer cross country race at Saturday's state championship at the Wamego Country Club golf course will certainly last more than 14 minutes.
Eudora senior Brittney Graff said if she's to win, to defend her Class 4A individual title and to knock off rival Heather Garcia of Baldwin, she's going to have to win approximately 140 10-second battles.
"My plan is to focus on staying with her for the next 10 seconds," Graff said. "After the first mile she tries to push the pace, and I need to stay up with her."
It makes for a fantastic story no matter how it is sliced.
Graff will likely have to run the best race of her life if she's to defend the title she won with ease a season ago.
Garcia was a middle of the pack runner at this time a year ago -- slowed by injuries -- and she was likely more worried about her team winning the state title than she was about a championship all of her own.
That was a lot of 10-second fights ago, however. Graff had a streak of seven-straight cross country wins snapped at the first meet this season. The streak snapper -- Garcia, of course.
It's been a reoccurring theme. The pair hasn't matched up at every week of the season, but when they have it's been the same story.
They both seemingly break from the main pack within a blink of the opening gun. Then they run side by side for mile after mile, one sometimes pushing a few steps ahead, but the other always answering.
And it has ended the same way every time. Garcia has pushed one too many times and Graff had fallen back.
Good luck getting Graff to cede her title as state champ, though.
As far as she's concerned, she's concerned she's only 140 battles and one sweet victory from another gold medal.
"I feel I'm a little stronger than last year," Graff said. "It's more fun this way. I like it a lot better with her there. It would be a lot more meaningful to win it this year because she's healthy.
"It would mean a lot more."
There's plenty of reason to think Graff can run down her opponent, too.
Garcia finished one minute, eight seconds behind Graff at state a year ago, but she finished 19 seconds ahead of her at the first meet of the season, an Aug. 31 race at Anderson County.
The gap widened by another second the next week at the Wamego Country Club golf course, where this weekend's state meet will take place, but ever since, Graff has been slowly closing.
Graff reeled off six-straight victories after the loss at Wamego, but fell again the next time she faced Garcia. The gap was again closer, however. Graff was 13 seconds back at league, then at Saturday's regional meet, Graff was only 10 seconds back.
"I still have my best race in me," Graff said. "I need to be confident in myself and stay focused on the race. Sometimes I get down on myself because she's beat me so many times, but I need to think the right way."
Graff will have plenty of supporters Saturday, and they won't all be watching her race either.
Graff led the way, but a strong performance across the board bought the Eudora girls team a ticket to state for the fifth-straight season.
Lauren Colman was 22nd, finishing the four-kilometer course in 17 minutes, 11 seconds. Emily Ballock was 28th in 17:28. Liz Hoese was 33rd in 17:57. Molly Brunton was 36th in 18:06 and Anne Marie Meyer-Myklestad was 48th in 18:39.
It all added up to third place.
The Cardinals finished with 112 points, well behind second-place Baldwin, but ahead of Basehor-Linwood's 125.
"Last year we came in and we were going after De Soto, but this year we had to battle it out for third," Ballock said. "We aren't as strong as we were last year, but we came together and we beat the people we needed to beat.
"It was a lot harder and we're all really excited."
The guys will have plenty on the line when they line up at state as well.
Joey Chino broke through to win the regional championship at Garnett, finishing the five-kilometer course in 16:55, eight seconds better than Baldwin's Chris Elniff.
"Joey's a competitive kid and he's put himself in a spot to vie for a state championship. I'm just really proud of him and happy for him and he's really worked his tail off to get to be where he's at.
Cody Burns also qualified as an individual for the second-straight year.
It was important to make it, he said. A disappointing showing at last year's state meet was on the mind during every sweaty summer workout, the senior said.
Now he has the opportunity to do something about it.
Burns was 11th in the race at 17:49.
"I just need to be more competitive in my second mile," Burns said. "All summer that's what was pushing me. I want to be in the top 20 and get a medal. I've never medaled in the state meet before."
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Many school districts and contractors are employing a variety of vehicles to supplement traditional yellow bus service. These alternative arrangements often cut costs and shorten ride times, but the safety implications of transporting students in taxis, vans and other non-school bus vehicles have become a contentious issue.
Like this Civil War-era luminary and others, bus drivers provide guidance to their passengers, and they are dedicated and care for those they work with and serve — all characteristics of a great leader.
Thorough bus inspections, pre-planning stops and operating the bus more slowly than usual will help to maximize driver and student safety. Areas on routes where drivers can pull over if necessary should be documented, and all stakeholders should maintain an open line of communication.
Being in a transportation management position can sometimes feel like being in between a rock and a hard place. However, directors who have effective working relationships with their unions say frequent communication, pitching in to build a team, and researching collective bargaining agreements help.
Intervention doesn't have to mean using physical force. Calling dispatch for help, stopping and securing the bus, and giving orders to the students are key steps in responding.
In this new feature, we spotlight dedicated women from around the nation ranging from school bus drivers, trainers and administrative assistants to bus company executives, directors of transportation and state directors whose work helps to keep students safe.
To shed some light on the personalities that make up the National Association for Pupil Transportation (NAPT) board of directors, the association has launched a series of board member profiles. Here, we hear from Dave McDonald, NAPT affiliate member director and director of business development and technical sales for Rosco Vision Systems.
Every summer, Terry Thomason, a dispatcher for Washington Elementary School District in Phoenix, travels to Minneapolis, where she and her mother and siblings volunteer for the Marmarth Research Foundation.
We have crossing guards to help students safely cross the street around schools. Why not have a built-in crossing guard on every school bus?
In the school bus industry, which has built an unparalleled safety record with its thorough driver requirements and strict vehicle construction standards, the thought of stepping outside of the school bus is disconcerting for many.
Get breaking news, industry updates, product announcements and more.
Shop at School Bus Store


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Aboriginal Health Workers Forum closing the gap
More than 100 Aboriginal health workers and other health professionals from across NSW will gather in Dubbo today, October 22, and tomorrow, October 23, for the annual Aboriginal Health Workforce Forum.
Western NSW Local Health District Manager Aboriginal Health Linda Williams said the forum has been a longstanding event in Western NSW with strong support from local health district executives.
"The forum endorses the commitment that our health district has to closing the gap on Aboriginal health disadvantage and provides a great opportunity to showcase the excellent work that has been happening across our district," Ms Williams said.