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(CNN) —  

The US-led coalition fighting ISIS in Syria conducted air and artillery strikes against pro-regime forces in Syria on Wednesday, killing an estimated 100 pro-regime fighters, according to a coalition statement.

The coalition described its action – which if confirmed could represent the largest number of pro-regime casualties inflicted by the US-led coalition – as carried out in “self defense.”

Syrian state news agency SANA described the action as an “aggression” by the coalition against “popular forces” who were fighting ISIS and the US-backed Syrian Democratic Forces. The attack had left “scores of persons dead and others injured” and caused “huge damage” to the area, SANA added.

According to a coalition statement, its strikes were carried out after forces allied with Syrian President Bashar al-Assad “initiated an unprovoked attack” against a well-established Syrian Democratic Forces headquarters where coalition advisers were working with US-backed Syrian fighters.

Some 500 pro-regime troops carried out the attack using artillery, mortar fire and Russian-made tanks “in what appears to be a coordinated attack on Syrian Democratic Forces,” US Army Col. Thomas Veale, a spokesman for the US-led coalition told CNN.

Veale said that about “20 to 30 artillery and tank rounds landed within 500 meters” of the Syrian Democratic Forces headquarters before the US-backed fighters and coalition forces “targeted the aggressors with a combination of air and artillery strikes.”

The US strikes were carried out by manned and unmanned aircraft as well as a US High Mobility Artillery Rocket System (HIMARS), two US military officials told CNN.

US F-22 stealth jets, F-15 fighters, and MQ-9 drones were involved in the counterattack according to US Air Forces Central Command.

“Along with ground based fire support, these aircraft released multiple precision fire munitions and conducted strafing runs against the aggressor force, stopping their advance and destroying multiple artillery pieces and tanks,” Lt. Col. Damien Pickart told CNN.

“We estimate more than 100 Syrian pro-regime forces were killed while engaging (Syrian Democratic Forces) and Coalition forces,” a US military official told CNN.

“This action was taken in self-defense,” Veale said, adding that pro-regime forces that returned across the river had not been targeted.

Veale said no coalition or US personnel had been killed or wounded in the engagement but that one member of the Syrian Democratic Forces was wounded.

The coalition said the attack took place in Khusham in the Middle Euphrates River Valley, five miles east of the agreed-on “de-confliction” line designed to separate Russian-backed regime troops and US-backed forces in Syria.

Veale said the coalition suspected that pro-regime forces were attempting to seize territory, including lucrative oil fields, that the Syrian Democratic Forces had liberated from ISIS in September.

They “were likely seeking to seize oilfields in Khusham that had been a major source of revenue for Daesh from 2014 to 2017,” he said, using the Arabic acronym for ISIS.

Russian hotline

Another US official who spoke to CNN said it was unclear exactly who the pro-regime forces were but that the US is looking into whether Russian contractors operating in the vicinity might have been involved. This official added that there is no direct evidence yet that the Russians had fired on the Syrian Democratic Forces facility where the US advisers were located. They have not ruled out that Iranian backed-forces might have also been involved in the attack, this official said.

Two US defense officials told CNN on Thursday that the US military now assesses that Russian contractors believed to be funded by the Russian government participated in Wednesday’s assault.

One official said that assessment is based on information obtained from monitoring communications in the area and from drone surveillance.

The second official said given the believed relationship between the contractors and the Russian government, it is difficult to imagine that Russian military forces in Syria were not aware of the contractors’ activities and involvement in the attack. That official also said the military assesses that some of the Russian contractors were killed in the US counterstrike.

The coalition “cannot speculate on the exact makeup of the Syrian pro-regime forces who conducted the attack at this time,” Veale said.

Veale said the coalition had informed Russia of the presence of pro-regime forces in the area before the attack via a hotline established as part of the de-confliction line agreement, adding that the coalition had observed a buildup of pro-regime troops over the past week.

“Coalition officials were in regular communication with Russian counterparts before, during and after the thwarted (Pro-Regime Forces) attack,” Veale said. “Russian officials assured Coalition officials they would not engage Coalition forces in the vicinity.”

Russia’s Ministry of Defense indicated Thursday that the pro-regime forces had not been coordinating with Russian officials in the area.

In a statement, the ministry said a “people’s militia of the pro-government forces” had come under mortar, rocket and helicopter fire from US-led coalition forces while conducting a “reconnaissance and search operation” near an oil refinery southeast of the town of Salhiyah.

“As a result of the shelling, 25 Syrian militias were injured,” the statement said. “The incident was caused by uncoordinated reconnaissance and search operations plans of the Syrian militias with the Russian command task force in the locality of Salhiyah.”

The US maintains about 2,000 troops in Syria, who mostly work with the over 50,000-strong Syrian Democratic Forces, a mix of Kurdish and Arab fighters who have been the primary US-backed force fighting ISIS in Syria.

This is not the first time the US military has clashed with pro-regime forces in Syria.

A US Navy F/A-18 shot down a Syrian regime Su-22 jet last June that had attacked US-backed forces on the ground. Coalition aircraft have struck regime forces who were perceived as posing a threat to a base at At Tanf, Syria, that houses US and coalition military advisers. The US also shot down a pro-regime drone after it dropped a munition in the vicinity of US troops in Syria.

CNN’s Mohammed Tawfeeq and Emma Burrows contributed to this report.